G protein-coupled receptors regulate diverse aspects of T-cell activity and effector function. Recently, we showed that GPR174 mediates the suppression of T-cell proliferation in vitro induced by the polar lipid lysophosphatidylserine (LysoPS). 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 GPR174 expression can constrain T-cell proliferation. In vitro experiments established that Gαs G proteins are needed for LysoPS/GPR174-mediated suppression of T-cell proliferation. Mechanistically, LysoPS acts via GPR174 and Gαs to suppress IL-2 production by activated T cells and limit upregulation of the activation markers CD25 and CD69. Together, our findings identify GPR174 as an abundantly expressed Gαs-dependent receptor that can negatively regulate naive T-cell activation. See also: News and Commentary by Robert & Mackay.

中文翻译：

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溶血磷脂酰丝氨酸通过 GPR174 抑制 T 细胞活化需要 Gαs 蛋白。

G 蛋白偶联受体调节 T 细胞活性和效应器功能的不同方面。最近，我们发现 GPR174 在体外介导由极性脂质溶血磷脂酰丝氨酸 (LysoPS) 诱导的 T 细胞增殖抑制。在这里，我们研究了该途径的体内活性并表征了所涉及的机制。使用亚致死辐射或调节性 T 细胞耗竭诱导的 T 细胞增殖的体内模型，我们表明 GPR174 表达可以限制 T 细胞增殖。体外实验证实，LysoPS/GPR174 介导的 T 细胞增殖抑制需要 Gαs G 蛋白。机制上，LysoPS 通过 GPR174 和 Gαs 抑制活化 T 细胞产生 IL-2 并限制活化标志物 CD25 和 CD69 的上调。一起，我们的研究结果确定 GPR174 是一种大量表达的 Gαs 依赖性受体，可以负调节幼稚 T 细胞活化。另见：Robert & Mackay 的新闻和评论。