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Efficient T‐cell priming and activation requires signaling through prostaglandin E2 (EP) receptors
Author(s) -
Sreeramkumar Vinatha,
Hons Miroslav,
Punzón Carmen,
Stein Jens V,
Sancho David,
Fresno Manuel,
Cuesta Natalia
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2015.62
Subject(s) - t cell , microbiology and biotechnology , priming (agriculture) , receptor , autocrine signalling , immune system , chemistry , biology , immunology , biochemistry , botany , germination
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.