Editors' ChoiceImmunology

Constraining regulatory T cells

See allHide authors and affiliations

Sci. Signal.  07 Jul 2015:
Vol. 8, Issue 384, pp. ec182
DOI: 10.1126/scisignal.aac9452

Regulatory CD4+ T cells (Tregs) maintain immune homeostasis by suppressing the activity of effector cells. The numbers and activity of Tregs are tightly controlled; too few Tregs could result in autoimmunity, whereas too many could prevent effective immune responses. Barnes et al. investigated the role of the lipid lysophosphatidylserine (LysoPS), which binds to the G protein–coupled receptor GPR174, in the development of Tregs. Flow cytometric analysis showed that mouse T cells expressed GPR174. Mice deficient in GPR174 had increased numbers of Tregs in the thymus and the periphery compared to those in wild-type mice. In vitro, LysoPS reduced the number of Tregs that differentiated from wild-type naïve T cells, but had no such effect on cultures of naïve T cells from GPR174-deficient mice. Compared with Tregs from wild-type mice, those from GPR174-deficient mice showed an enhanced ability to suppress the proliferation of stimulated naïve CD4+ T cells in vitro. Liquid chromatography followed by tandem mass spectrometry analysis showed the presence of LysoPS isoforms in the thymus, lymph nodes, and the colon of mice. Gene expression analysis revealed that mRNA encoding a LysoPS-synthesizing enzyme was abundant in various immune cells and in lymphoid organs. In mice with the inflammatory condition experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, deficiency in GPR174 resulted in reduced disease severity. Together, these data demonstrate that LysoPS through GPR174 inhibits both the activity of Tregs and their increase in number, suggesting that receptor antagonists might act as therapies to treat autoimmune diseases.

M. J. Barnes, C.-M. Li, Y. Xu, J. An, Y. Huang, J. G. Cyster, The lysophosphatidylserine receptor GPR174 constrains regulatory T cell development and function. J. Exp. Med. 212, 1011–1020 (2015). [PubMed]

Correction (9 July 2015): There was an error in the text. In the original sentence, "Compared with Tregs from wild-type mice, those from GPR174-deficient mice showed a reduced ability to suppress the proliferation of stimulated naïve CD4+ T cells in vitro," the word "reduced" was mistakenly used. It should instead read "enhanced." This has been corrected.