Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland.
Translational Gastroenterology Unit, NDM Experimental Medicine, University of Oxford, Oxford, UK.
Nat Immunol. 2018 Oct;19(10):1126-1136. doi: 10.1038/s41590-018-0200-5. Epub 2018 Sep 10.
Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. Here we characterized two human CD4 T17 helper cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10 T17 cells upregulated a variety of genes encoding immunoregulatory molecules, as well as genes whose expression is characteristic of tissue-resident T cells. In contrast, IL-10 T17 cells maintained a pro-inflammatory gene-expression profile and upregulated the expression of homing receptors that guide recirculation from tissues to blood. Expression of the transcription factor c-MAF was selectively upregulated in IL-10 T17 cells, and it was bound to a large set of enhancer-like regions and modulated the immunoregulatory and tissue-residency program. Our results identify c-MAF as a relevant factor that drives two highly divergent post-activation fates of human T17 cells and provide a framework with which to investigate the role of these cells in physiology and immunopathology.
不同类型的效应器和记忆 T 淋巴细胞在保护性或病理性免疫反应中被诱导和维持。在这里，我们描述了两种人类 CD4 T17 辅助细胞亚群，在最近激活的状态下，可以根据其表达抗炎细胞因子 IL-10 来区分。IL-10 T17 细胞上调了多种编码免疫调节分子的基因，以及表达特征为组织驻留 T 细胞的基因。相比之下，IL-10 T17 细胞保持了促炎基因表达谱，并上调了引导从组织到血液再循环的归巢受体的表达。转录因子 c-MAF 的表达在 IL-10 T17 细胞中被选择性地上调，它与一大组增强子样区域结合，并调节免疫调节和组织驻留程序。我们的结果表明 c-MAF 是一个相关的因素，它驱动人类 T17 细胞两种高度不同的激活后命运，并为研究这些细胞在生理学和免疫病理学中的作用提供了一个框架。
