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REV-ERB agonist suppresses IL-17 production in gamma delta T cells and improves psoriatic dermatitis in a mouse model

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Title: REV-ERB agonist suppresses IL-17 production in gamma delta T cells and improves psoriatic dermatitis in a mouse model
Authors: Wang, Shangyi Browse this author
Kozai, Mina Browse this author
Mita, Hironobu Browse this author
Cai, Zimeng Browse this author
Masum, Md Abdul Browse this author
Ichii, Osamu Browse this author →KAKEN DB
Takada, Kensuke Browse this author →KAKEN DB
Inaba, Mutsumi Browse this author →KAKEN DB
Keywords: IL-17
gamma delta T cells
Nuclear receptor
Issue Date: 7-Oct-2021
Publisher: Elsevier
Journal Title: Biomedicine & pharmacotherapy
Volume: 144
Start Page: 112283
Publisher DOI: 10.1016/j.biopha.2021.112283
Abstract: 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.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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