Retineic-acid-receptor-related orphan nuclear receptor gamma (RORγt) is considered to be one of the master regulators in the development of T helper 17 cells (Th17 cells), which have an essential role in the development of many autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis (1). RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ thymocytes. Therefore, RORγt is selectively expressed in the thymus and other immune system tissues although RORγt mRNA is detected in many tissues (2,3). Regulatory T cells can co-express RORγt and FOXP3 and are shown to be both pro-inflammatory and immunosuppressive (4). Studies have also shown a subset of CD8+RORγt+ T cells expressing a low level of PD-1 and a high level of OX40 were associated with reduced patient survival thus CD8+RORγt+ T cells are proinflammatory (5). RORγt seems to be a key regulator of immune homeostasis, proinflammatory, and may have potential for therapeutic targets in inflammatory diseases (6).
1. Zhang Y, et al. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2015; 36:71–87.
2. Guo Y, et al. Inhibition of RORγT Skewes TCR α Gene Rearrangement and Limits T Cell Repertoire Diversity. Cell Rep. 2016; 17:3206-3218.
3. Eberl G, et al. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol. 2004; 5:64–73.
4. Chellappa S, et al. Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer. Oncoimmunology. 2015; 29:5:e1102828.
5. Chellappa S, et al. CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer. J Immunol. 2017; 198:1729-1739.
6. Ivanov II, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006; 126:1121-1133.
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