期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 144, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112283
关键词
IL-17; gamma delta T cells; Psoriasis; Nuclear receptor; REV-ERB
资金
- MEXT/JSPS [17H03928, 21H02375]
- World-leading Innovative and Smart Education Program from the MEXT [1801]
- MEXT [JPMXS0420100619]
- Grants-in-Aid for Scientific Research [21H02375, 17H03928] Funding Source: KAKEN
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and cellular infiltration. Recent research has highlighted the crucial role of gamma delta T17 cells in psoriasis pathogenesis, revealing their involvement in regulation through REV-ERBs. Synthetic REV-ERB agonists can suppress gamma delta T17 cells both in vitro and in vivo, providing a novel therapeutic approach for psoriasis targeting REV-ERBs in gamma delta T17 cells.
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and cellular infiltration. Studies have shown that disease development depends on proinflammatory cytokines, such as interleukin (IL)-23 and IL-17. It has been suggested that IL-23 produced by innate immune cells, such as macrophages, stimulates a subset of helper T cells to release IL-17, promoting neutrophil recruitment and keratinocyte proliferation. However, recent studies have revealed the crucial role of gamma delta T cells in psoriasis pathogenesis as the primary source of dermal IL-17. The nuclear receptors REV-ERBs are ligand-dependent transcription factors recognized as circadian rhythm regulators. REV-ERBs negatively regulate IL-17-producing helper T cells, whereas the involvement of REV-ERBs in regulating IL-17-producing gamma delta T (gamma delta T17) cells remains unclear. Here we revealed the regulatory mechanism involving gamma delta T17 cells through REV-ERBs. gamma delta T17 cell levels were remarkably elevated in the secondary lymphoid organs of mice that lacked an isoform of REV-ERBs. A synthetic REV-ERB agonist, 5R9009, suppressed gamma delta T17 cells in vitro and in vivo. Topical application of SR9009 to the skin reduced the inflammatory symptoms of psoriasiform dermatitis in mice. The results of this study provide a novel therapeutic approach for psoriasis targeting REV-ERBs in gamma delta T17 cells.
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