Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation [bulk RNA-seq]. Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation [bulk RNA-seq]

Regulatory T (Treg) cells represent a specialized CD4+ T cell lineage with essential anti-inflammatory functions. Recent studies of the adaptations of Treg cells to non-lymphoid tissues which enable their specialized immunosuppressive and tissue supportive functions raise questions about the underlying mechanisms of these adaptations and whether they represent stable differentiation or reversible activation states. Using novel genetic tools, we characterized the transcriptional programs of distinct colonic effector Treg cell types. We found that attenuated T cell receptor (TCR) signaling and acquisition of substantial TCR independent functionality appears to facilitate the terminal differentiation of a population of colonic effector Treg cells distinguished by stable expression of immunomodulatory cytokine interleukin-10 (IL-10). Functional studies revealed that this subset of effector Treg cells, but not their expression of IL-10, was indispensable for preventing colitis. These findings suggest core features of terminal differentiation of effector Treg cells in non-lymphoid tissues and their function therein. Overall design: Comparative gene expression of colonic Treg cells expressing Il10, not expressing Il10 and with a history of Il10 expression (3 paired biological replicates)

调节性T（Treg）细胞是一类特化的CD4+ T细胞谱系，具备核心的抗炎功能。近年来针对Treg细胞适应非淋巴组织的研究表明，此类适应过程赋予其特化的免疫抑制与组织支持功能，但其背后的潜在调控机制尚不明确，且此类适应究竟属于稳定分化还是可逆激活状态仍有待探究。本研究借助新型遗传工具，对不同结肠效应性Treg细胞亚型的转录程序进行了系统表征。我们发现，减弱的T细胞受体（T cell receptor，TCR）信号转导与获得的显著TCR非依赖性功能，似乎可促进一群以稳定表达免疫调节细胞因子白细胞介素-10（IL-10）为特征的结肠效应性Treg细胞群体的终末分化。功能实验结果显示，该效应性Treg细胞亚群（而非其IL-10的表达）对于预防结肠炎不可或缺。上述研究结果揭示了非淋巴组织中效应性Treg细胞终末分化的核心特征及其在组织内的功能机制。实验整体设计：对表达Il10、不表达Il10以及有Il10表达历史的结肠Treg细胞进行比较基因表达分析（3组配对生物学重复）