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Lysophosphatidylserine suppression of T‐cell activation via GPR 174 requires Gαs proteins
Author(s) -
Barnes Michael J,
Cyster Jason G
Publication year - 2018
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 - 10.1111/imcb.12025
Subject(s) - microbiology and biotechnology , downregulation and upregulation , cell growth , receptor , effector , t cell , cell , in vivo , signal transduction , biology , in vitro , function (biology) , chemistry , biochemistry , immunology , immune system , gene
G protein‐coupled receptors regulate diverse aspects of T‐cell activity and effector function. Recently, we showed that GPR 174 mediates the suppression of T‐cell proliferation in vitro induced by the polar lipid lysophosphatidylserine (Lyso PS ). Here, we investigated the in vivo activity of this pathway and characterized the mechanisms involved. Using in vivo models of T‐cell proliferation induced by sublethal irradiation or regulatory T‐cell depletion, we show that GPR 174 expression can constrain T‐cell proliferation. In vitro experiments established that Gαs G proteins are needed for Lyso PS / GPR 174‐mediated suppression of T‐cell proliferation. Mechanistically, Lyso PS acts via GPR 174 and Gαs to suppress IL ‐2 production by activated T cells and limit upregulation of the activation markers CD 25 and CD 69. Together, our findings identify GPR 174 as an abundantly expressed Gαs‐dependent receptor that can negatively regulate naive T‐cell activation. See also: News and Commentary by Robert & Mackay.