{"oa_version":"None","intvolume":"        94","publist_id":"6116","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","volume":94,"date_created":"2018-12-11T11:50:46Z","publisher":"Nature Publishing Group","year":"2016","scopus_import":1,"title":"Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors","quality_controlled":"1","status":"public","acknowledgement":"This manuscript has been supported by grants SAF2007-61716 and S-SAL-0159/2006 awarded by the Spanish Ministry of Science and Education and the Community of Madrid to Dr M Fresno.","type":"journal_article","doi":"10.1038/icb.2015.62","page":"39 - 51","author":[{"last_name":"Sreeramkumar","first_name":"Vinatha","full_name":"Sreeramkumar, Vinatha"},{"orcid":"0000-0002-6625-3348","last_name":"Hons","first_name":"Miroslav","full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carmen","last_name":"Punzón","full_name":"Punzón, Carmen"},{"last_name":"Stein","first_name":"Jens","full_name":"Stein, Jens"},{"last_name":"Sancho","first_name":"David","full_name":"Sancho, David"},{"first_name":"Manuel","last_name":"Fresno Forcelledo","full_name":"Fresno Forcelledo, Manuel"},{"last_name":"Cuesta","first_name":"Natalia","full_name":"Cuesta, Natalia"}],"day":"01","publication":"Immunology and Cell Biology","month":"01","date_updated":"2021-01-12T06:49:09Z","citation":{"short":"V. Sreeramkumar, M. Hons, C. Punzón, J. Stein, D. Sancho, M. Fresno Forcelledo, N. Cuesta, Immunology and Cell Biology 94 (2016) 39–51.","chicago":"Sreeramkumar, Vinatha, Miroslav Hons, Carmen Punzón, Jens Stein, David Sancho, Manuel Fresno Forcelledo, and Natalia Cuesta. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” <i>Immunology and Cell Biology</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/icb.2015.62\">https://doi.org/10.1038/icb.2015.62</a>.","ista":"Sreeramkumar V, Hons M, Punzón C, Stein J, Sancho D, Fresno Forcelledo M, Cuesta N. 2016. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. 94(1), 39–51.","apa":"Sreeramkumar, V., Hons, M., Punzón, C., Stein, J., Sancho, D., Fresno Forcelledo, M., &#38; Cuesta, N. (2016). Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. <i>Immunology and Cell Biology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/icb.2015.62\">https://doi.org/10.1038/icb.2015.62</a>","ama":"Sreeramkumar V, Hons M, Punzón C, et al. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. <i>Immunology and Cell Biology</i>. 2016;94(1):39-51. doi:<a href=\"https://doi.org/10.1038/icb.2015.62\">10.1038/icb.2015.62</a>","ieee":"V. Sreeramkumar <i>et al.</i>, “Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors,” <i>Immunology and Cell Biology</i>, vol. 94, no. 1. Nature Publishing Group, pp. 39–51, 2016.","mla":"Sreeramkumar, Vinatha, et al. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” <i>Immunology and Cell Biology</i>, vol. 94, no. 1, Nature Publishing Group, 2016, pp. 39–51, doi:<a href=\"https://doi.org/10.1038/icb.2015.62\">10.1038/icb.2015.62</a>."},"date_published":"2016-01-01T00:00:00Z","publication_status":"published","issue":"1","department":[{"_id":"MiSi"}],"language":[{"iso":"eng"}],"_id":"1217","abstract":[{"text":"Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E 2 (PGE 2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE 2 during T-cell receptor stimulation. In addition, we show that autocrine PGE 2 signaling through EP receptors is essential for optimal CD4 + T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE 2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4 + Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE 2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE 2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings.","lang":"eng"}]}