Research Institute of Women's Health, Sookmyung Women's University, Seoul 04310; Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul 04310, Korea.
Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul 04310, Korea.
BMB Rep. 2023 May;56(5):296-301. doi: 10.5483/BMBRep.2022-0169.
Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocytespecific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.as an adjuvant for cancer immunotherapy. [BMB Reports 2023; 56(5): 296-301].
维甲酸受体相关孤儿受体α（RORα）在多种生理过程中发挥着重要作用，包括代谢、癌症、昼夜节律、小脑发育和炎症。虽然 RORα在皮肤中表达，但它在皮肤生理学中的作用仍未得到充分阐明。在此，Rorα在表皮的基底层和上基底层表达；然而，角质形成细胞特异性的 Rorα 缺失并不影响正常的表皮形成。在病理生理条件下，Rorα 缺陷型小鼠表现出银屑病样症状的缓解，包括表皮分层相对完整、角质形成细胞过度增殖减少以及角质形成细胞中炎症细胞因子的低水平表达。出乎意料的是，角质形成细胞特异性 RORα 缺失小鼠的脾 Th17 细胞群明显低于对照组。此外，Rorα 缺失减少了咪喹莫特诱导的角质形成细胞核因子-κB 和 STAT3 的激活。因此，我们预计 RORα 抑制剂将作用于免疫细胞和角质形成细胞，以抑制银屑病的发生和进展。[BMB 报告 2023；56(5): 296-301]。
