J Clin Invest. 2023 Jan 3;133(1):e166019. doi: 10.1172/JCI166019.
Type I regulatory T (Tr1) cells are a population of regulatory CD4+ T cells implicated in the suppression of pathological immune responses across multiple diseases, but a unifying transcriptional signature of Tr1 identity across disease contexts has not been characterized. In this issue of the JCI, Edward, Ng, and colleagues identified a conserved transcriptional signature that distinguished Tr1 (IL-10+IFN-γ+) from Th1 (IL-10-IFN-γ+) cells in human and mouse malaria. This signature implicated genes encoding inhibitory receptors - including CTLA-4 and LAG-3 - and transcription factors - including cMAF. The authors identified coinhibitory receptor expression that distinguished Tr1 cells from other CD4+ T cell subsets. Furthermore, cMAF - and, to a lesser extent, BLIMP-1 - promoted IL-10 production in human CD4+ T cells. BLIMP-1 also played a role in supporting the expression of inhibitory receptors. These findings describe a few key features that seem to be conserved by Tr1 cells across multiple species, disease contexts, and marker definitions.
I 型调节性 T（Tr1）细胞是一种调节性 CD4+T 细胞群体，参与多种疾病中病理性免疫反应的抑制，但在不同疾病背景下，Tr1 身份的统一转录特征尚未得到描述。在本期 JCI 中，Edward、Ng 和同事们鉴定出一个保守的转录特征，可将人类和鼠疟中的 Tr1（IL-10+IFN-γ+）与 Th1（IL-10-IFN-γ+）细胞区分开来。该特征涉及编码抑制性受体的基因 - 包括 CTLA-4 和 LAG-3 - 和转录因子 - 包括 cMAF。作者鉴定出可区分 Tr1 细胞与其他 CD4+T 细胞亚群的共抑制受体表达。此外，cMAF - 以及在较小程度上 BLIMP-1 - 促进了人类 CD4+T 细胞中 IL-10 的产生。BLIMP-1 也在支持抑制性受体的表达中发挥作用。这些发现描述了一些关键特征，似乎在多种物种、疾病背景和标记物定义中被 Tr1 细胞保守。
