RORs 及其配体在（病理）生理学中的作用。
Action of RORs and their ligands in (patho)physiology.
机构信息
The Scripps Research Institute, Jupiter, FL 33458, USA.
出版信息
Trends Endocrinol Metab. 2012 Dec;23(12):619-27. doi: 10.1016/j.tem.2012.05.012. Epub 2012 Jul 11.
Abstract
The retinoic-acid-receptor-related orphan receptors (RORs) are members of the nuclear receptor (NR) superfamily whose activity has been implicated in several physiological and pathological processes. The RORs, specifically RORα and RORγ, are considered to be master regulators of T(H)17 cells, a recently described subset of CD4(+) T helper cells that have been demonstrated to have a pathological role in autoimmune disease. As with most members of the NR superfamily, RORs are ligand-regulated, suggesting that their activity can be modulated by synthetic ligands. Recent advances in the field have established that selective inhibition of the RORs is a viable therapeutic approach for not only the treatment of autoimmune disorders but also ROR-mediated metabolic disorders.
摘要
维甲酸受体相关孤儿受体（RORs）是核受体（NR）超家族的成员，其活性被认为与多种生理和病理过程有关。RORs，特别是 RORα 和 RORγ，被认为是 T(H)17 细胞的主要调节因子，T(H)17 细胞是最近描述的 CD4(+)辅助性 T 细胞亚群，已被证明在自身免疫性疾病中具有病理作用。与 NR 超家族的大多数成员一样，RORs 是配体调节的，这表明它们的活性可以通过合成配体来调节。该领域的最新进展表明，ROR 选择性抑制不仅是治疗自身免疫性疾病的可行治疗方法，也是 ROR 介导的代谢紊乱的可行治疗方法。
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2
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PLoS One. 2012;7(4):e34921. doi: 10.1371/journal.pone.0034921. Epub 2012 Apr 11.
3
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4
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Ann N Y Acad Sci. 2012 Jan;1247:34-45. doi: 10.1111/j.1749-6632.2011.06355.x. Epub 2012 Jan 12.
5
Th17 cell cytokine secretion profile in host defense and autoimmunity.辅助性 T 细胞 17 细胞细胞因子分泌谱在宿主防御和自身免疫中的作用。
Inflamm Res. 2012 Feb;61(2):87-96. doi: 10.1007/s00011-011-0419-1. Epub 2011 Dec 25.
6
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Cell. 2011 Sep 2;146(5):772-84. doi: 10.1016/j.cell.2011.07.033. Epub 2011 Aug 25.
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10
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J Clin Invest. 2011 Jun;121(6):2133-41. doi: 10.1172/JCI46043. Epub 2011 Jun 1.
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