Retinoic acid-related orphan receptor γt (RORγt) functions as a ligand-dependent transcription factor that regulates multiple proinflammatory genes and plays a critical role in several inflammatory and autoimmune diseases. Various endogenous and synthetic RORγ (inverse) agonists have been identified that regulate RORγ transcriptional activity, including many cholesterol intermediates and oxysterols. Changes in cholesterol biosynthesis and metabolism can therefore have a significant impact on the generation of oxysterol RORγ ligands and, consequently, can control RORγt activity and inflammation. These observations contribute to a growing literature that connects cholesterol metabolism to the regulation of immune responses and autoimmune disease. Loss of RORγ function in knockout mice and in mice treated with RORγ inverse agonists results in reduced production of proinflammatory cytokines, such as IL-17A/F, and increased resistance to autoimmune disease in several experimental rodent models. Thus, RORγt inverse agonists might provide an attractive therapeutic approach to treat a variety of autoimmune diseases.

中文翻译：

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与视黄酸有关的孤儿受体激动剂（反向）：调节免疫反应，炎症和自身免疫性疾病。

维甲酸相关的孤儿受体γt（RORγt）作为配体依赖性转录因子，可调节多个促炎基因，并在多种炎症和自身免疫性疾病中发挥关键作用。已经确定了各种内源性和合成的RORγ（反向）激动剂，它们调节RORγ的转录活性，包括许多胆固醇中间体和氧固醇。因此，胆固醇生物合成和代谢的变化可能会对氧固醇RORγ配体的产生产生重大影响，因此可以控制RORγt的活性和炎症。这些观察为越来越多的文献做出了贡献，这些文献将胆固醇代谢与免疫反应和自身免疫性疾病的调节联系起来。在敲除小鼠和用RORγ反向激动剂治疗的小鼠中RORγ功能的丧失导致促炎细胞因子（如IL-17A / F）的产生减少，并且在一些实验性啮齿动物模型中增加了对自身免疫疾病的抵抗力。因此，RORγt反向激动剂可能提供一种有吸引力的治疗方法，以治疗多种自身免疫性疾病。