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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Alleviation of imiquimod-induced psoriasis-like symptoms in Rorα-deficient mouse skin

  • Koog Chan Park (Research Institute of Women's Health, Sookmyung Women's University) ;
  • Jiwon Kim (Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women's University) ;
  • Aram Lee (Research Institute of Women's Health, Sookmyung Women's University) ;
  • Jong-Seok Lim (Research Institute of Women's Health, Sookmyung Women's University) ;
  • Keun Il Kim (Research Institute of Women's Health, Sookmyung Women's University)
  • Received : 2022.10.24
  • Accepted : 2023.01.25
  • Published : 2023.05.31
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Abstract

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 keratinocyte-specific 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.

Keywords

Acknowledgement

This work was supported by the Science Research Center Program (Cellular Heterogeneity Research Center, NRF-RS-2023-00207857) to KIK, and by the Basic Science Research Program (2020R111A1A01068126) to KCP, through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT).

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