article published yes Vinatha Sreeramkumar author Miroslav Hons author 4167FE56-F248-11E8-B48F-1D18A9856A870000-0002-6625-3348 Carmen Punzón author Jens Stein author David Sancho author Manuel Fresno Forcelledo author Natalia Cuesta author MiSi department 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. Nature Publishing Group2016 eng 00036762860000510.1038/icb.2015.62 94139 - 51 V. Sreeramkumar, M. Hons, C. Punzón, J. Stein, D. Sancho, M. Fresno Forcelledo, N. Cuesta, Immunology and Cell Biology 94 (2016) 39–51. 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>. 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. 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> 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> 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>. 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. 12172018-12-11T11:50:46Z2025-09-22T09:34:26Z