Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Pathol. 2020 Oct;190(10):1984-1999. doi: 10.1016/j.ajpath.2020.07.010. Epub 2020 Jul 29.
Retinoic acid-related orphan receptor (ROR)-γt, the master transcription factor of the Th17 subset of CD4 Th cells, is a promising target for treating a host of autoimmune diseases. RORγt plays a vital role in the pathogenesis of inflammatory bowel diseases-Crohn disease and ulcerative colitis-caused by untoward reactivity of the immune system to the components of the intestinal microbiome. The mammalian intestinal tract is a highly complex and compartmentalized organ with specialized functions, and is a privileged site for the generation of both peripherally induced regulatory CD4 T cells (Tregs) and effector Th17 cells. As Th17 cells can be proinflammatory in nature, the equilibrium between effector Th17 and Treg cells is crucial for balancing intestinal homeostasis and inflammation. Recent findings suggest that RORγt, in addition to Th17 cells, is also expressed in peripherally induced, colonic regulatory CD4 T cells. Therefore, RORγt is expressed in both effector and regulatory subsets of CD4 T cells in the intestine. The present review discusses the role of RORγt in cellular and molecular differentiation of Th17 and Treg, and examines how targeting RORγt in inflammatory bowel disease therapy could influence the development of these two diverse subsets of immune cells with opposing functions.
维甲酸相关孤儿受体（ROR）-γt 是 CD4 Th 细胞 Th17 亚群的主要转录因子，是治疗多种自身免疫性疾病的有前途的靶点。RORγt 在由免疫系统对肠道微生物组成分的不当反应引起的炎症性肠病-Crohn 病和溃疡性结肠炎的发病机制中起着至关重要的作用。哺乳动物肠道是一个高度复杂和分隔的器官，具有专门的功能，是外周诱导的调节性 CD4 T 细胞（Tregs）和效应 Th17 细胞产生的特权部位。由于 Th17 细胞本质上可以是促炎的，因此效应 Th17 和 Treg 细胞之间的平衡对于平衡肠道内稳态和炎症至关重要。最近的研究结果表明，除了 Th17 细胞外，RORγt 还在外周诱导的结肠调节性 CD4 T 细胞中表达。因此，RORγt 在肠道中的效应和调节性 CD4 T 细胞亚群中均有表达。本文综述了 RORγt 在 Th17 和 Treg 细胞的细胞和分子分化中的作用，并探讨了靶向炎症性肠病治疗中的 RORγt 如何影响这两种具有相反功能的免疫细胞的不同亚群的发展。
