---
_id: '13052'
abstract:
- lang: eng
text: Imaging of the immunological synapse (IS) between dendritic cells (DCs) and
T cells in suspension is hampered by suboptimal alignment of cell-cell contacts
along the vertical imaging plane. This requires optical sectioning that often
results in unsatisfactory resolution in time and space. Here, we present a workflow
where DCs and T cells are confined between a layer of glass and polydimethylsiloxane
(PDMS) that orients the cells along one, horizontal imaging plane, allowing for
fast en-face-imaging of the DC-T cell IS.
acknowledged_ssus:
- _id: Bio
- _id: NanoFab
- _id: M-Shop
acknowledgement: 'A.L. was funded by an Erwin Schrödinger postdoctoral fellowship
of the Austrian Science Fund (FWF, project number: J4542-B) and is an EMBO non-stipendiary
postdoctoral fellow. This work was supported by a European Research Council grant
ERC-CoG-72437 to M.S. We thank the Imaging & Optics facility, the Nanofabrication
facility, and the Miba Machine Shop of ISTA for their excellent support.'
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: 'Leithner AF, Merrin J, Sixt MK. En-Face Imaging of T Cell-Dendritic Cell Immunological
Synapses. In: Baldari C, Dustin M, eds. The Immune Synapse. Vol 2654. MIMB.
New York, NY: Springer Nature; 2023:137-147. doi:10.1007/978-1-0716-3135-5_9'
apa: 'Leithner, A. F., Merrin, J., & Sixt, M. K. (2023). En-Face Imaging of
T Cell-Dendritic Cell Immunological Synapses. In C. Baldari & M. Dustin (Eds.),
The Immune Synapse (Vol. 2654, pp. 137–147). New York, NY: Springer Nature.
https://doi.org/10.1007/978-1-0716-3135-5_9'
chicago: 'Leithner, Alexander F, Jack Merrin, and Michael K Sixt. “En-Face Imaging
of T Cell-Dendritic Cell Immunological Synapses.” In The Immune Synapse,
edited by Cosima Baldari and Michael Dustin, 2654:137–47. MIMB. New York, NY:
Springer Nature, 2023. https://doi.org/10.1007/978-1-0716-3135-5_9.'
ieee: 'A. F. Leithner, J. Merrin, and M. K. Sixt, “En-Face Imaging of T Cell-Dendritic
Cell Immunological Synapses,” in The Immune Synapse, vol. 2654, C. Baldari
and M. Dustin, Eds. New York, NY: Springer Nature, 2023, pp. 137–147.'
ista: 'Leithner AF, Merrin J, Sixt MK. 2023.En-Face Imaging of T Cell-Dendritic
Cell Immunological Synapses. In: The Immune Synapse. Methods in Molecular Biology,
vol. 2654, 137–147.'
mla: Leithner, Alexander F., et al. “En-Face Imaging of T Cell-Dendritic Cell Immunological
Synapses.” The Immune Synapse, edited by Cosima Baldari and Michael Dustin,
vol. 2654, Springer Nature, 2023, pp. 137–47, doi:10.1007/978-1-0716-3135-5_9.
short: A.F. Leithner, J. Merrin, M.K. Sixt, in:, C. Baldari, M. Dustin (Eds.), The
Immune Synapse, Springer Nature, New York, NY, 2023, pp. 137–147.
date_created: 2023-05-22T08:41:48Z
date_published: 2023-04-28T00:00:00Z
date_updated: 2023-10-17T08:44:53Z
day: '28'
department:
- _id: MiSi
- _id: NanoFab
doi: 10.1007/978-1-0716-3135-5_9
ec_funded: 1
editor:
- first_name: Cosima
full_name: Baldari, Cosima
last_name: Baldari
- first_name: Michael
full_name: Dustin, Michael
last_name: Dustin
external_id:
pmid:
- '37106180'
intvolume: ' 2654'
language:
- iso: eng
month: '04'
oa_version: None
page: 137-147
place: New York, NY
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: The Immune Synapse
publication_identifier:
eisbn:
- '9781071631355'
eissn:
- 1940-6029
isbn:
- '9781071631348'
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
series_title: MIMB
status: public
title: En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2654
year: '2023'
...
---
_id: '10703'
abstract:
- lang: eng
text: 'When crawling through the body, leukocytes often traverse tissues that are
densely packed with extracellular matrix and other cells, and this raises the
question: How do leukocytes overcome compressive mechanical loads? Here, we show
that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness
requires neither force sensing via the nucleus nor adhesive interactions with
a substrate. Upon global compression of the cell body as well as local indentation
of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into
dot-like structures, providing activation platforms for Arp2/3 nucleated actin
patches. These patches locally push against the external load, which can be obstructing
collagen fibers or other cells, and thereby create space to facilitate forward
locomotion. We show in vitro and in vivo that this WASp function is rate limiting
for ameboid leukocyte migration in dense but not in loose environments and is
required for trafficking through diverse tissues such as skin and lymph nodes.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner
for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes
Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll
for advice on fluorescent labeling of collagen gels. This research was supported
by the Scientific Service Units (SSUs) of IST Austria through resources provided
by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron
Microscopy Facility. This work was funded by grants from the European Research Council
( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding
from the European Union’s Horizon 2020 research and innovation program under the
Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Gaertner, Florian
last_name: Gaertner
- first_name: Patricia
full_name: Reis-Rodrigues, Patricia
last_name: Reis-Rodrigues
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Juan
full_name: Aguilera, Juan
last_name: Aguilera
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive
actin patches to facilitate immune cell migration in dense tissues. Developmental
Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024
apa: Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl,
M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate
immune cell migration in dense tissues. Developmental Cell. Cell Press ;
Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024
chicago: Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons,
Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive
Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental
Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024.
ieee: F. Gaertner et al., “WASp triggers mechanosensitive actin patches to
facilitate immune cell migration in dense tissues,” Developmental Cell,
vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.
ista: Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner
AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK.
2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues. Developmental Cell. 57(1), 47–62.e9.
mla: Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to
Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell,
vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.
short: F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl,
A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild,
M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.
date_created: 2022-01-30T23:01:33Z
date_published: 2022-01-10T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '10'
ddc:
- '570'
department:
- _id: MiSi
- _id: EM-Fac
- _id: NanoFab
- _id: BjHo
doi: 10.1016/j.devcel.2021.11.024
ec_funded: 1
external_id:
isi:
- '000768933800005'
pmid:
- '34919802'
intvolume: ' 57'
isi: 1
issue: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
url: https://www.sciencedirect.com/science/article/pii/S1534580721009497
month: '01'
oa: 1
oa_version: Published Version
page: 47-62.e9
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: Developmental Cell
publication_identifier:
eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Cell Press ; Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 57
year: '2022'
...
---
_id: '11843'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein
located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids
involved in CD14 binding are highly conserved across pathogenic and non-pathogenic
strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration
by overactivation of integrins and blunted expression of co-stimulatory molecules
by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
rate-limiting factors of T cell activation. This response was binary at the single-cell
level, but averaged in larger populations exposed to both piliated and non-piliated
pathogens, presumably via the exchange of immunomodulatory cytokines. While defining
an active molecular mechanism of immune evasion by pathogens, the interaction
between FimH and CD14 represents a potential target to interfere with persistent
and recurrent infections, such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89,
and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and
Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and
Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific
Service Units, especially the Bioimaging facility, the Preclinical facility and
the Electron microscopy facility for technical support, Jakob Wallner and all members
of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically
reading the manuscript. This work was supported by grants from the Austrian Research
Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373),
and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
eLife. 2022;11. doi:10.7554/eLife.78995
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.78995
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences
Publications, 2022. https://doi.org/10.7554/eLife.78995.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
to CD14. eLife. 11, e78995.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife
Sciences Publications, 2022, doi:10.7554/eLife.78995.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
ELife 11 (2022).
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2023-08-03T12:54:21Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
file:
- access_level: open_access
checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-16T08:57:37Z
date_updated: 2022-08-16T08:57:37Z
file_id: '11861'
file_name: 2022_eLife_Tomasek.pdf
file_size: 2057577
relation: main_file
success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '10316'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
_id: '9094'
abstract:
- lang: eng
text: Dendritic cells (DCs) are crucial for the priming of naive T cells and the
initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell
contact, the immunological synapse (IS). While it is established that F-actin
dynamics regulates signaling at the T cell side of the contact, little is known
about the cytoskeletal contribution on the DC side. Here, we show that the DC
actin cytoskeleton is decisive for the formation of a multifocal synaptic structure,
which correlates with T cell priming efficiency. DC actin at the IS appears in
transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence
of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase
in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of
activated and proliferating T cells, demonstrating an important role for DC actin
in the regulation of immune synapse functionality.
article_number: e202006081
article_processing_charge: No
article_type: original
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: LM
full_name: Altenburger, LM
last_name: Altenburger
- first_name: R
full_name: Hauschild, R
last_name: Hauschild
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: K
full_name: Rottner, K
last_name: Rottner
- first_name: Stradal
full_name: TEB, Stradal
last_name: TEB
- first_name: A
full_name: Diz-Muñoz, A
last_name: Diz-Muñoz
- first_name: JV
full_name: Stein, JV
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Leithner AF, Altenburger L, Hauschild R, et al. Dendritic cell actin dynamics
control contact duration and priming efficiency at the immunological synapse.
Journal of Cell Biology. 2021;220(4). doi:10.1083/jcb.202006081
apa: Leithner, A. F., Altenburger, L., Hauschild, R., Assen, F. P., Rottner, K.,
TEB, S., … Sixt, M. K. (2021). Dendritic cell actin dynamics control contact duration
and priming efficiency at the immunological synapse. Journal of Cell Biology.
Rockefeller University Press. https://doi.org/10.1083/jcb.202006081
chicago: Leithner, Alexander F, LM Altenburger, R Hauschild, Frank P Assen, K Rottner,
Stradal TEB, A Diz-Muñoz, JV Stein, and Michael K Sixt. “Dendritic Cell Actin
Dynamics Control Contact Duration and Priming Efficiency at the Immunological
Synapse.” Journal of Cell Biology. Rockefeller University Press, 2021.
https://doi.org/10.1083/jcb.202006081.
ieee: A. F. Leithner et al., “Dendritic cell actin dynamics control contact
duration and priming efficiency at the immunological synapse,” Journal of Cell
Biology, vol. 220, no. 4. Rockefeller University Press, 2021.
ista: Leithner AF, Altenburger L, Hauschild R, Assen FP, Rottner K, TEB S, Diz-Muñoz
A, Stein J, Sixt MK. 2021. Dendritic cell actin dynamics control contact duration
and priming efficiency at the immunological synapse. Journal of Cell Biology.
220(4), e202006081.
mla: Leithner, Alexander F., et al. “Dendritic Cell Actin Dynamics Control Contact
Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell
Biology, vol. 220, no. 4, e202006081, Rockefeller University Press, 2021,
doi:10.1083/jcb.202006081.
short: A.F. Leithner, L. Altenburger, R. Hauschild, F.P. Assen, K. Rottner, S. TEB,
A. Diz-Muñoz, J. Stein, M.K. Sixt, Journal of Cell Biology 220 (2021).
date_created: 2021-02-05T10:08:04Z
date_published: 2021-04-05T00:00:00Z
date_updated: 2023-09-05T13:57:53Z
day: '05'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1083/jcb.202006081
external_id:
isi:
- '000626365700001'
pmid:
- '33533935'
file:
- access_level: open_access
checksum: 843ebc153847c8626e13c9c5ce71d533
content_type: application/pdf
creator: dernst
date_created: 2022-05-12T14:16:21Z
date_updated: 2022-05-12T14:16:21Z
file_id: '11367'
file_name: 2021_JournCellBiology_Leithner.pdf
file_size: 5102328
relation: main_file
success: 1
file_date_updated: 2022-05-12T14:16:21Z
has_accepted_license: '1'
intvolume: ' 220'
isi: 1
issue: '4'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
issn:
- 0021-9525
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dendritic cell actin dynamics control contact duration and priming efficiency
at the immunological synapse
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 220
year: '2021'
...
---
_id: '10316'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on dendritic cells as a previously undescribed binding partner of FimH,
the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH
amino acids involved in CD14 binding are highly conserved across pathogenic and
non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced
dendritic cell migration and blunted expression of co-stimulatory molecules, both
rate-limiting factors of T cell activation. While defining an active molecular
mechanism of immune evasion by pathogens, the interaction between FimH and CD14
represents a potential target to interfere with persistent and recurrent infections,
such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra
and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments
and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis.
We thank the IST Austria Scientific Service Units, especially the Bioimaging facility,
the Preclinical facility and the Electron microscopy facility for technical support,
Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions
and Daria Siekhaus for critically reading the manuscript. This work was supported
by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G.,
the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911)
to M.S.
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv. doi:10.1101/2021.10.18.464770
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2021.10.18.464770
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv, 10.1101/2021.10.18.464770.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2021.10.18.464770.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
BioRxiv (n.d.).
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2024-03-25T23:30:19Z
day: '18'
department:
- _id: CaGu
- _id: MiSi
doi: 10.1101/2021.10.18.464770
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '11843'
relation: later_version
status: public
- id: '10307'
relation: dissertation_contains
status: public
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_id: '323'
abstract:
- lang: eng
text: 'In the here presented thesis, we explore the role of branched actin networks
in cell migration and antigen presentation, the two most relevant processes in
dendritic cell biology. Branched actin networks construct lamellipodial protrusions
at the leading edge of migrating cells. These are typically seen as adhesive structures,
which mediate force transduction to the extracellular matrix that leads to forward
locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found
that the resulting cells lack lamellipodial protrusions. Instead, depending on
the maturation state, one or multiple filopodia were formed. By challenging these
cells in a variety of migration assays we found that lamellipodial protrusions
are dispensable for the locomotion of leukocytes and actually dampen the speed
of migration. However, lamellipodia are critically required to negotiate complex
environments that DCs experience while they travel to the next draining lymph
node. Taken together our results suggest that leukocyte lamellipodia have rather
a sensory- than a force transducing function. Furthermore, we show for the first
time structure and dynamics of dendritic cell F-actin at the immunological synapse
with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated
by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension,
leading to an altered ultrastructure of the immunological synapse and severe T
cell priming defects. These results point towards a previously unappreciated role
of the cellular mechanics of dendritic cells in T cell activation. Additionally,
we present a novel cell culture based system for the differentiation of dendritic
cells from conditionally immortalized hematopoietic precursors. These precursor
cells are genetically tractable via the CRISPR/Cas9 system while they retain their
ability to differentiate into highly migratory dendritic cells and other immune
cells. This will foster the study of all aspects of dendritic cell biology and
beyond. '
acknowledged_ssus:
- _id: NanoFab
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: "First of all I would like to thank Michael Sixt for giving me the
opportunity to work in \r\nhis group and for his support throughout the years. He
is a truly inspiring person and \r\nthe best boss one can imagine. I would
\ also like to thank all current and past \r\nmembers of the Sixt group for
their help and the great working atmosphere in the lab. \r\nIt is a true privilege
to work with such a bright, funny and friendly group of people and \r\nI’m proud
\ that I could be part of it. Furthermore, I would like to say ‘thank
\ you’ to Daria Siekhaus for all the meetings and discussion we had throughout
the years \r\nand to Federica Benvenuti for being part of my committee.
\ I am also grateful to Jack \r\nMerrin in the nanofabrication facility
\ and all the people working in the bioimaging-\r\n, the electron microscopy-
and the preclinical facilities."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
citation:
ama: Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:10.15479/AT:ISTA:th_998
apa: Leithner, A. F. (2018). Branched actin networks in dendritic cell biology.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_998
chicago: Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_998.
ieee: A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute
of Science and Technology Austria, 2018.
ista: Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute
of Science and Technology Austria.
mla: Leithner, Alexander F. Branched Actin Networks in Dendritic Cell Biology.
Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_998.
short: A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute
of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:45:49Z
date_published: 2018-04-12T00:00:00Z
date_updated: 2023-09-07T12:39:44Z
day: '12'
ddc:
- '571'
- '599'
- '610'
degree_awarded: PhD
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:th_998
file:
- access_level: closed
checksum: d5e3edbac548c26c1fa43a4b37a54a4c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-05T09:23:11Z
date_updated: 2021-02-11T23:30:17Z
embargo_to: open_access
file_id: '6219'
file_name: PhD_thesis_AlexLeithner_final_version.docx
file_size: 29027671
relation: source_file
- access_level: open_access
checksum: 071f7476db29e41146824ebd0697cb10
content_type: application/pdf
creator: dernst
date_created: 2019-04-05T09:23:11Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-04-15
file_id: '6220'
file_name: PhD_thesis_AlexLeithner.pdf
file_size: 66045341
relation: main_file
file_date_updated: 2021-02-11T23:30:17Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '99'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7542'
pubrep_id: '998'
related_material:
record:
- id: '1321'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: Branched actin networks in dendritic cell biology
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '15'
abstract:
- lang: eng
text: Although much is known about the physiological framework of T cell motility,
and numerous rate-limiting molecules have been identified through loss-of-function
approaches, an integrated functional concept of T cell motility is lacking. Here,
we used in vivo precision morphometry together with analysis of cytoskeletal dynamics
in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic
organs. We show that the contributions of the integrin LFA-1 and the chemokine
receptor CCR7 are complementary rather than positioned in a linear pathway, as
they are during leukocyte extravasation from the blood vasculature. Our data demonstrate
that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction
that is sufficient to drive locomotion in the absence of considerable surface
adhesions and plasma membrane flux.
acknowledged_ssus:
- _id: SSU
acknowledgement: This work was funded by grants from the European Research Council
(ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S.
and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457
and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon
2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement
no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).
article_processing_charge: No
author:
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Jens
full_name: Stein, Jens
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently
tune actin flow and substrate friction during intranodal migration of T cells.
Nature Immunology. 2018;19(6):606-616. doi:10.1038/s41590-018-0109-z
apa: Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J.,
… Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and
substrate friction during intranodal migration of T cells. Nature Immunology.
Nature Publishing Group. https://doi.org/10.1038/s41590-018-0109-z
chicago: Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian
R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines
and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal
Migration of T Cells.” Nature Immunology. Nature Publishing Group, 2018.
https://doi.org/10.1038/s41590-018-0109-z.
ieee: M. Hons et al., “Chemokines and integrins independently tune actin
flow and substrate friction during intranodal migration of T cells,” Nature
Immunology, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.
ista: Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J,
Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow
and substrate friction during intranodal migration of T cells. Nature Immunology.
19(6), 606–616.
mla: Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow
and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology,
vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:10.1038/s41590-018-0109-z.
short: M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz,
J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.
date_created: 2018-12-11T11:44:10Z
date_published: 2018-05-18T00:00:00Z
date_updated: 2024-03-25T23:30:22Z
day: '18'
department:
- _id: MiSi
- _id: Bio
doi: 10.1038/s41590-018-0109-z
ec_funded: 1
external_id:
isi:
- '000433041500026'
pmid:
- '29777221'
intvolume: ' 19'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/29777221
month: '05'
oa: 1
oa_version: Published Version
page: 606 - 616
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1396-2014
name: Molecular and system level view of immune cell migration
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Nature Immunology
publication_status: published
publisher: Nature Publishing Group
publist_id: '8040'
quality_controlled: '1'
related_material:
record:
- id: '6891'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Chemokines and integrins independently tune actin flow and substrate friction
during intranodal migration of T cells
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 19
year: '2018'
...
---
_id: '153'
abstract:
- lang: eng
text: Cells migrating in multicellular organisms steadily traverse complex three-dimensional
(3D) environments. To decipher the underlying cell biology, current experimental
setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or
in vivo environments. While only in vivo experiments are truly physiological,
they do not allow for precise manipulation of environmental parameters. 2D in
vitro experiments do allow mechanical and chemical manipulations, but increasing
evidence demonstrates substantial differences of migratory mechanisms in 2D and
3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate
cell migration in complex but fully controllable 3D environments. Pillar forests
are polydimethylsiloxane-based setups, in which two closely adjacent surfaces
are interconnected by arrays of micrometer-sized pillars. Changing the pillar
shape, size, height and the inter-pillar distance precisely manipulates microenvironmental
parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily
combined with chemotactic cues, surface coatings, diverse cell types and advanced
imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration
assays with the precise definition of 3D environmental parameters.
article_processing_charge: No
author:
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: 'Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. Micro-engineered
“pillar forests” to study cell migration in complex but controlled 3D environments.
In: Methods in Cell Biology. Vol 147. Academic Press; 2018:79-91. doi:10.1016/bs.mcb.2018.07.004'
apa: Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., & Sixt, M. K.
(2018). Micro-engineered “pillar forests” to study cell migration in complex but
controlled 3D environments. In Methods in Cell Biology (Vol. 147, pp. 79–91).
Academic Press. https://doi.org/10.1016/bs.mcb.2018.07.004
chicago: Renkawitz, Jörg, Anne Reversat, Alexander F Leithner, Jack Merrin, and
Michael K Sixt. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in
Complex but Controlled 3D Environments.” In Methods in Cell Biology, 147:79–91.
Academic Press, 2018. https://doi.org/10.1016/bs.mcb.2018.07.004.
ieee: J. Renkawitz, A. Reversat, A. F. Leithner, J. Merrin, and M. K. Sixt, “Micro-engineered
‘pillar forests’ to study cell migration in complex but controlled 3D environments,”
in Methods in Cell Biology, vol. 147, Academic Press, 2018, pp. 79–91.
ista: 'Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. 2018.Micro-engineered
“pillar forests” to study cell migration in complex but controlled 3D environments.
In: Methods in Cell Biology. vol. 147, 79–91.'
mla: Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration
in Complex but Controlled 3D Environments.” Methods in Cell Biology, vol.
147, Academic Press, 2018, pp. 79–91, doi:10.1016/bs.mcb.2018.07.004.
short: J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods
in Cell Biology, Academic Press, 2018, pp. 79–91.
date_created: 2018-12-11T11:44:54Z
date_published: 2018-07-27T00:00:00Z
date_updated: 2023-09-13T08:56:35Z
day: '27'
department:
- _id: MiSi
- _id: NanoFab
doi: 10.1016/bs.mcb.2018.07.004
external_id:
isi:
- '000452412300006'
pmid:
- '30165964'
intvolume: ' 147'
isi: 1
language:
- iso: eng
month: '07'
oa_version: None
page: 79 - 91
pmid: 1
publication: Methods in Cell Biology
publication_identifier:
issn:
- 0091679X
publication_status: published
publisher: Academic Press
publist_id: '7768'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Micro-engineered “pillar forests” to study cell migration in complex but controlled
3D environments
type: book_chapter
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 147
year: '2018'
...
---
_id: '402'
abstract:
- lang: eng
text: During metastasis, malignant cells escape the primary tumor, intravasate lymphatic
vessels, and reach draining sentinel lymph nodes before they colonize distant
organs via the blood circulation. Although lymph node metastasis in cancer patients
correlates with poor prognosis, evidence is lacking as to whether and how tumor
cells enter the bloodstream via lymph nodes. To investigate this question, we
delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells
into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated
the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without
involvement of the thoracic duct. These results suggest that the lymph node blood
vessels can serve as an exit route for systemic dissemination of cancer cells
in experimental mouse models. Whether this form of tumor cell spreading occurs
in cancer patients remains to be determined.
acknowledged_ssus:
- _id: Bio
acknowledgement: "M.B. was supported by the Cell Communication in Health and Disease
graduate study program of the Austrian Science Fund (FWF) and the Medical University
of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556)
and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic
injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster
and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri
for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging,
the Sixt lab for intellectual input, M. Schunn for help with the design of the in
vivo experiments, F. Langer for technical assistance with the in vivo experiments,
the bioimaging facility of IST Austria for support, and R. Efferl for providing
the CT26 cell line."
article_processing_charge: No
article_type: original
author:
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Helga
full_name: Schachner, Helga
last_name: Schachner
- first_name: Gabriele
full_name: Asfour, Gabriele
last_name: Asfour
- first_name: Zsuzsanna
full_name: Bagó Horváth, Zsuzsanna
last_name: Bagó Horváth
- first_name: Jens
full_name: Stein, Jens
last_name: Stein
- first_name: Pavel
full_name: Uhrin, Pavel
last_name: Uhrin
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
citation:
ama: Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit
routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411.
doi:10.1126/science.aal3662
apa: Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G.,
… Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic
tumor cell dissemination in mice. Science. American Association for the
Advancement of Science. https://doi.org/10.1126/science.aal3662
chicago: Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner,
Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide
Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science.
American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662.
ieee: M. Brown et al., “Lymph node blood vessels provide exit routes for
metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382.
American Association for the Advancement of Science, pp. 1408–1411, 2018.
ista: Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth
Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide
exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382),
1408–1411.
mla: Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic
Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American
Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.
short: M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z.
Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018)
1408–1411.
date_created: 2018-12-11T11:46:16Z
date_published: 2018-03-23T00:00:00Z
date_updated: 2024-03-25T23:30:05Z
day: '23'
department:
- _id: MiSi
doi: 10.1126/science.aal3662
ec_funded: 1
external_id:
isi:
- '000428043600047'
pmid:
- '29567714'
intvolume: ' 359'
isi: 1
issue: '6382'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1126/science.aal3662
month: '03'
oa: 1
oa_version: Published Version
page: 1408 - 1411
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7428'
quality_controlled: '1'
related_material:
record:
- id: '6947'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination
in mice
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 359
year: '2018'
...
---
_id: '437'
abstract:
- lang: eng
text: Dendritic cells (DCs) are sentinels of the adaptive immune system that reside
in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation
and up-regulate the chemokine receptor CCR7 that guides them along gradients of
its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs
present peripherally acquired antigen to naïve T cells, thereby triggering adaptive
immunity.
acknowledged_ssus:
- _id: SSU
acknowledgement: "This work was supported by grants of the European Research Council
(ERC CoG 724373) and the Austrian Science Fund (FWF) to M.S. We thank the scientific
support units at IST Austria for excellent technical support.\r\nWe thank the scientific
\ support units at IST Austria for excellent technical support. "
article_processing_charge: Yes (via OA deal)
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Hans
full_name: Haecker, Hans
last_name: Haecker
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. Fast
and efficient genetic engineering of hematopoietic precursor cells for the study
of dendritic cell migration. European Journal of Immunology. 2018;48(6):1074-1077.
doi:10.1002/eji.201747358
apa: Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., &
Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor
cells for the study of dendritic cell migration. European Journal of Immunology.
Wiley-Blackwell. https://doi.org/10.1002/eji.201747358
chicago: Leithner, Alexander F, Jörg Renkawitz, Ingrid de Vries, Robert Hauschild,
Hans Haecker, and Michael K Sixt. “Fast and Efficient Genetic Engineering of Hematopoietic
Precursor Cells for the Study of Dendritic Cell Migration.” European Journal
of Immunology. Wiley-Blackwell, 2018. https://doi.org/10.1002/eji.201747358.
ieee: A. F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, and M.
K. Sixt, “Fast and efficient genetic engineering of hematopoietic precursor cells
for the study of dendritic cell migration,” European Journal of Immunology,
vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.
ista: Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. 2018.
Fast and efficient genetic engineering of hematopoietic precursor cells for the
study of dendritic cell migration. European Journal of Immunology. 48(6), 1074–1077.
mla: Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic
Precursor Cells for the Study of Dendritic Cell Migration.” European Journal
of Immunology, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:10.1002/eji.201747358.
short: A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K.
Sixt, European Journal of Immunology 48 (2018) 1074–1077.
date_created: 2018-12-11T11:46:28Z
date_published: 2018-02-13T00:00:00Z
date_updated: 2023-09-11T14:01:18Z
day: '13'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.1002/eji.201747358
ec_funded: 1
external_id:
isi:
- '000434963700016'
file:
- access_level: open_access
checksum: 9d5b74cd016505aeb9a4c2d33bbedaeb
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:56Z
date_updated: 2020-07-14T12:46:27Z
file_id: '5044'
file_name: IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf
file_size: 590106
relation: main_file
file_date_updated: 2020-07-14T12:46:27Z
has_accepted_license: '1'
intvolume: ' 48'
isi: 1
issue: '6'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '02'
oa: 1
oa_version: Published Version
page: 1074 - 1077
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: European Journal of Immunology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '7386'
pubrep_id: '1067'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast and efficient genetic engineering of hematopoietic precursor cells for
the study of dendritic cell migration
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 48
year: '2018'
...
---
_id: '672'
abstract:
- lang: eng
text: Trafficking cells frequently transmigrate through epithelial and endothelial
monolayers. How monolayers cooperate with the penetrating cells to support their
transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic
capillaries as a model system for transendothelial migration. We find that the
chemokine CCL21, which is the decisive guidance cue for intravasation, mainly
localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial
cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes
extracellularly enriched at the sites of endothelial cell-cell junctions. When
we reconstitute the transmigration process in vitro, we find that secretion of
CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and
selective calcium chelation in lymphatic endothelium attenuates transmigration.
Altogether, our data demonstrate a chemokine-mediated feedback between DCs and
lymphatic endothelium, which facilitates transendothelial migration.
article_processing_charge: Yes
author:
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Matthias
full_name: Mehling, Matthias
id: 3C23B994-F248-11E8-B48F-1D18A9856A87
last_name: Mehling
orcid: 0000-0001-8599-1226
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the
chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia.
Cell Reports. 2017;19(5):902-909. doi:10.1016/j.celrep.2017.04.027
apa: Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling,
M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes
dendritic cell transmigration across lymphatic endothelia. Cell Reports.
Cell Press. https://doi.org/10.1016/j.celrep.2017.04.027
chicago: Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander
F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered
Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic
Endothelia.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.027.
ieee: K. Vaahtomeri et al., “Locally triggered release of the chemokine CCL21
promotes dendritic cell transmigration across lymphatic endothelia,” Cell Reports,
vol. 19, no. 5. Cell Press, pp. 902–909, 2017.
ista: Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann
W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic
cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.
mla: Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21
Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports,
vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:10.1016/j.celrep.2017.04.027.
short: K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling,
W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.
date_created: 2018-12-11T11:47:50Z
date_published: 2017-05-02T00:00:00Z
date_updated: 2023-02-23T12:50:09Z
day: '02'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1016/j.celrep.2017.04.027
ec_funded: 1
file:
- access_level: open_access
checksum: 8fdddaab1f1d76a6ec9ca94dcb6b07a2
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:54Z
date_updated: 2020-07-14T12:47:38Z
file_id: '5109'
file_name: IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf
file_size: 2248814
relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: ' 19'
issue: '5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 902 - 909
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Cell Reports
publication_identifier:
issn:
- '22111247'
publication_status: published
publisher: Cell Press
publist_id: '7052'
pubrep_id: '900'
quality_controlled: '1'
scopus_import: 1
status: public
title: Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration
across lymphatic endothelia
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 19
year: '2017'
...
---
_id: '674'
abstract:
- lang: eng
text: Navigation of cells along gradients of guidance cues is a determining step
in many developmental and immunological processes. Gradients can either be soluble
or immobilized to tissues as demonstrated for the haptotactic migration of dendritic
cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate
how gradient characteristics govern cellular response patterns, we here introduce
an in vitro system allowing to track migratory responses of DCs to precisely controlled
immobilized gradients of CCL21. We find that haptotactic sensing depends on the
absolute CCL21 concentration and local steepness of the gradient, consistent with
a scenario where DC directionality is governed by the signal-to-noise ratio of
CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC
guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore,
we find that CCR7 signal termination by the G-protein-coupled receptor kinase
6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient
sensing in vitro and confirm those observations in vivo. These findings suggest
that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal
guidance in vivo.
author:
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Veronika
full_name: Bierbaum, Veronika
id: 3FD04378-F248-11E8-B48F-1D18A9856A87
last_name: Bierbaum
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Teresa
full_name: Tarrant, Teresa
last_name: Tarrant
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic
chemokine gradients in a manner governed by signal to noise ratio and dependent
on GRK6. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004
apa: Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries,
I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients
in a manner governed by signal to noise ratio and dependent on GRK6. Current
Biology. Cell Press. https://doi.org/10.1016/j.cub.2017.04.004
chicago: Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus
Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret
Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio
and Dependent on GRK6.” Current Biology. Cell Press, 2017. https://doi.org/10.1016/j.cub.2017.04.004.
ieee: J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine
gradients in a manner governed by signal to noise ratio and dependent on GRK6,”
Current Biology, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.
ista: Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner
AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells
interpret haptotactic chemokine gradients in a manner governed by signal to noise
ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.
mla: Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients
in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current
Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004.
short: J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries,
A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt,
Current Biology 27 (2017) 1314–1325.
date_created: 2018-12-11T11:47:51Z
date_published: 2017-05-09T00:00:00Z
date_updated: 2023-02-23T12:50:44Z
day: '09'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1016/j.cub.2017.04.004
ec_funded: 1
intvolume: ' 27'
issue: '9'
language:
- iso: eng
month: '05'
oa_version: None
page: 1314 - 1325
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Current Biology
publication_identifier:
issn:
- '09609822'
publication_status: published
publisher: Cell Press
publist_id: '7050'
quality_controlled: '1'
scopus_import: 1
status: public
title: Dendritic cells interpret haptotactic chemokine gradients in a manner governed
by signal to noise ratio and dependent on GRK6
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2017'
...
---
_id: '5567'
abstract:
- lang: eng
text: Immunological synapse DC-Tcells
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
citation:
ama: Leithner AF. Immunological synapse DC-Tcells. 2017. doi:10.15479/AT:ISTA:71
apa: Leithner, A. F. (2017). Immunological synapse DC-Tcells. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:71
chicago: Leithner, Alexander F. “Immunological Synapse DC-Tcells.” Institute of
Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:71.
ieee: A. F. Leithner, “Immunological synapse DC-Tcells.” Institute of Science and
Technology Austria, 2017.
ista: Leithner AF. 2017. Immunological synapse DC-Tcells, Institute of Science and
Technology Austria, 10.15479/AT:ISTA:71.
mla: Leithner, Alexander F. Immunological Synapse DC-Tcells. Institute of
Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:71.
short: A.F. Leithner, (2017).
datarep_id: '71'
date_created: 2018-12-12T12:31:34Z
date_published: 2017-08-09T00:00:00Z
date_updated: 2024-02-21T13:47:00Z
day: '09'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:71
file:
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checksum: 3d6942d47d0737d064706b5728c4d8c8
content_type: video/x-msvideo
creator: system
date_created: 2018-12-12T13:02:47Z
date_updated: 2020-07-14T12:47:04Z
file_id: '5612'
file_name: IST-2017-71-v1+1_Synapse_1.avi
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date_created: 2018-12-12T13:02:51Z
date_updated: 2020-07-14T12:47:04Z
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file_size: 226232496
relation: main_file
file_date_updated: 2020-07-14T12:47:04Z
has_accepted_license: '1'
keyword:
- Immunological synapse
license: https://creativecommons.org/publicdomain/zero/1.0/
month: '08'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
status: public
title: Immunological synapse DC-Tcells
tmp:
image: /images/cc_0.png
legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
name: Creative Commons Public Domain Dedication (CC0 1.0)
short: CC0 (1.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2017'
...
---
_id: '1321'
abstract:
- lang: eng
text: Most migrating cells extrude their front by the force of actin polymerization.
Polymerization requires an initial nucleation step, which is mediated by factors
establishing either parallel filaments in the case of filopodia or branched filaments
that form the branched lamellipodial network. Branches are considered essential
for regular cell motility and are initiated by the Arp2/3 complex, which in turn
is activated by nucleation-promoting factors of the WASP and WAVE families. Here
we employed rapid amoeboid crawling leukocytes and found that deletion of the
WAVE complex eliminated actin branching and thus lamellipodia formation. The cells
were left with parallel filaments at the leading edge, which translated, depending
on the differentiation status of the cell, into a unipolar pointed cell shape
or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased
speed and enormous directional persistence, while they were unable to turn towards
chemotactic gradients. Cells with multiple filopodia retained chemotactic activity
but their migration was progressively impaired with increasing geometrical complexity
of the extracellular environment. These findings establish that diversified leading
edge protrusions serve as explorative structures while they slow down actual locomotion.
acknowledged_ssus:
- _id: SSU
acknowledgement: "This work was supported by the German Research Foundation (DFG)
Priority Program SP 1464 to T.E.B.S. and M.S., and European Research Council (ERC
GA 281556) and Human Frontiers Program grants to M.S.\r\nService Units of IST Austria
for excellent technical support."
article_processing_charge: No
article_type: original
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Alexander
full_name: Eichner, Alexander
id: 4DFA52AE-F248-11E8-B48F-1D18A9856A87
last_name: Eichner
- first_name: Jan
full_name: Müller, Jan
id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D
last_name: Müller
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: David
full_name: De Gorter, David
last_name: De Gorter
- first_name: Florian
full_name: Schur, Florian
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Jonathan
full_name: Bayerl, Jonathan
last_name: Bayerl
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Stefan
full_name: Wieser, Stefan
id: 355AA5A0-F248-11E8-B48F-1D18A9856A87
last_name: Wieser
orcid: 0000-0002-2670-2217
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Frank
full_name: Lai, Frank
last_name: Lai
- first_name: Markus
full_name: Moser, Markus
last_name: Moser
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Victor
full_name: Small, Victor
last_name: Small
- first_name: Theresia
full_name: Stradal, Theresia
last_name: Stradal
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Leithner AF, Eichner A, Müller J, et al. Diversified actin protrusions promote
environmental exploration but are dispensable for locomotion of leukocytes. Nature
Cell Biology. 2016;18:1253-1259. doi:10.1038/ncb3426
apa: Leithner, A. F., Eichner, A., Müller, J., Reversat, A., Brown, M., Schwarz,
J., … Sixt, M. K. (2016). Diversified actin protrusions promote environmental
exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology.
Nature Publishing Group. https://doi.org/10.1038/ncb3426
chicago: Leithner, Alexander F, Alexander Eichner, Jan Müller, Anne Reversat, Markus
Brown, Jan Schwarz, Jack Merrin, et al. “Diversified Actin Protrusions Promote
Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature
Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/ncb3426.
ieee: A. F. Leithner et al., “Diversified actin protrusions promote environmental
exploration but are dispensable for locomotion of leukocytes,” Nature Cell
Biology, vol. 18. Nature Publishing Group, pp. 1253–1259, 2016.
ista: Leithner AF, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J,
De Gorter D, Schur FK, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai F, Moser
M, Kerjaschki D, Rottner K, Small V, Stradal T, Sixt MK. 2016. Diversified actin
protrusions promote environmental exploration but are dispensable for locomotion
of leukocytes. Nature Cell Biology. 18, 1253–1259.
mla: Leithner, Alexander F., et al. “Diversified Actin Protrusions Promote Environmental
Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell
Biology, vol. 18, Nature Publishing Group, 2016, pp. 1253–59, doi:10.1038/ncb3426.
short: A.F. Leithner, A. Eichner, J. Müller, A. Reversat, M. Brown, J. Schwarz,
J. Merrin, D. De Gorter, F.K. Schur, J. Bayerl, I. de Vries, S. Wieser, R. Hauschild,
F. Lai, M. Moser, D. Kerjaschki, K. Rottner, V. Small, T. Stradal, M.K. Sixt,
Nature Cell Biology 18 (2016) 1253–1259.
date_created: 2018-12-11T11:51:21Z
date_published: 2016-10-24T00:00:00Z
date_updated: 2024-03-25T23:30:09Z
day: '24'
ddc:
- '570'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
doi: 10.1038/ncb3426
ec_funded: 1
file:
- access_level: open_access
checksum: e1411cb7c99a2d9089c178a6abef25e7
content_type: application/pdf
creator: dernst
date_created: 2020-05-14T16:33:46Z
date_updated: 2020-07-14T12:44:43Z
file_id: '7844'
file_name: 2018_NatureCell_Leithner.pdf
file_size: 4433280
relation: main_file
file_date_updated: 2020-07-14T12:44:43Z
has_accepted_license: '1'
intvolume: ' 18'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 1253 - 1259
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Nature Cell Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '5949'
quality_controlled: '1'
related_material:
record:
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relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: Diversified actin protrusions promote environmental exploration but are dispensable
for locomotion of leukocytes
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 18
year: '2016'
...