---
_id: '9259'
abstract:
- lang: eng
  text: Gradients of chemokines and growth factors guide migrating cells and morphogenetic
    processes. Migration of antigen-presenting dendritic cells from the interstitium
    into the lymphatic system is dependent on chemokine CCL21, which is secreted by
    endothelial cells of the lymphatic capillary, binds heparan sulfates and forms
    gradients decaying into the interstitium. Despite the importance of CCL21 gradients,
    and chemokine gradients in general, the mechanisms of gradient formation are unclear.
    Studies on fibroblast growth factors have shown that limited diffusion is crucial
    for gradient formation. Here, we used the mouse dermis as a model tissue to address
    the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the
    formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic
    endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels
    at the lymphatic capillaries and did neither affect interstitial CCL21 gradient
    shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan
    sulfates at the level of the lymphatic endothelium are dispensable for the formation
    of a functional CCL21 gradient.
acknowledgement: "This work was supported by Sigrid Juselius fellowship (KV), University
  of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding
  (315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the
  Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen
  is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for
  providing the conditional Ext1 mouse strain."
article_number: '630002'
article_processing_charge: No
article_type: original
author:
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Christine
  full_name: Moussion, Christine
  id: 3356F664-F248-11E8-B48F-1D18A9856A87
  last_name: Moussion
- 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: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial
    chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic
    endothelium. <i>Frontiers in Immunology</i>. 2021;12. doi:<a href="https://doi.org/10.3389/fimmu.2021.630002">10.3389/fimmu.2021.630002</a>
  apa: Vaahtomeri, K., Moussion, C., Hauschild, R., &#38; Sixt, M. K. (2021). Shape
    and function of interstitial chemokine CCL21 gradients are independent of heparan
    sulfates produced by lymphatic endothelium. <i>Frontiers in Immunology</i>. Frontiers.
    <a href="https://doi.org/10.3389/fimmu.2021.630002">https://doi.org/10.3389/fimmu.2021.630002</a>
  chicago: Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt.
    “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent
    of Heparan Sulfates Produced by Lymphatic Endothelium.” <i>Frontiers in Immunology</i>.
    Frontiers, 2021. <a href="https://doi.org/10.3389/fimmu.2021.630002">https://doi.org/10.3389/fimmu.2021.630002</a>.
  ieee: K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function
    of interstitial chemokine CCL21 gradients are independent of heparan sulfates
    produced by lymphatic endothelium,” <i>Frontiers in Immunology</i>, vol. 12. Frontiers,
    2021.
  ista: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of
    interstitial chemokine CCL21 gradients are independent of heparan sulfates produced
    by lymphatic endothelium. Frontiers in Immunology. 12, 630002.
  mla: Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21
    Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.”
    <i>Frontiers in Immunology</i>, vol. 12, 630002, Frontiers, 2021, doi:<a href="https://doi.org/10.3389/fimmu.2021.630002">10.3389/fimmu.2021.630002</a>.
  short: K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology
    12 (2021).
date_created: 2021-03-21T23:01:20Z
date_published: 2021-02-25T00:00:00Z
date_updated: 2023-08-07T14:18:26Z
day: '25'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.3389/fimmu.2021.630002
ec_funded: 1
external_id:
  isi:
  - '000627134400001'
  pmid:
  - '33717158'
file:
- access_level: open_access
  checksum: 663f5a48375e42afa4bfef58d42ec186
  content_type: application/pdf
  creator: dernst
  date_created: 2021-03-22T12:08:26Z
  date_updated: 2021-03-22T12:08:26Z
  file_id: '9277'
  file_name: 2021_FrontiersImmumo_Vaahtomeri.pdf
  file_size: 3740146
  relation: main_file
  success: 1
file_date_updated: 2021-03-22T12:08:26Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Frontiers in Immunology
publication_identifier:
  eissn:
  - 1664-3224
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Shape and function of interstitial chemokine CCL21 gradients are independent
  of heparan sulfates produced by lymphatic endothelium
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: 12
year: '2021'
...