REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model
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...
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doaj-550fd90ff8164fe1becb6007a39dfb222021-10-09T04:36:47ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-12-01144112283REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse modelShangyi Wang0Mina Kozai1Hironobu Mita2Zimeng Cai3Md. Abdul Masum4Osamu Ichii5Kensuke Takada6Mutsumi Inaba7Laboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Anatomy, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Anatomy, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, JapanLaboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Correspondence to: Laboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, N18W9 Kita-ku, Sapporo 060-0818, Japan.Laboratory of Molecular Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanPsoriasis 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 γδT 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 γδT (γδT17) cells remains unclear. Here we revealed the regulatory mechanism involving γδT17 cells through REV-ERBs. γδT17 cell levels were remarkably elevated in the secondary lymphoid organs of mice that lacked an isoform of REV-ERBs. A synthetic REV-ERB agonist, SR9009, suppressed γδT17 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 γδT17 cells.http://www.sciencedirect.com/science/article/pii/S0753332221010672IL-17γδT cellsPsoriasisNuclear receptorREV-ERB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shangyi Wang Mina Kozai Hironobu Mita Zimeng Cai Md. Abdul Masum Osamu Ichii Kensuke Takada Mutsumi Inaba |
spellingShingle |
Shangyi Wang Mina Kozai Hironobu Mita Zimeng Cai Md. Abdul Masum Osamu Ichii Kensuke Takada Mutsumi Inaba REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model Biomedicine & Pharmacotherapy IL-17 γδT cells Psoriasis Nuclear receptor REV-ERB |
author_facet |
Shangyi Wang Mina Kozai Hironobu Mita Zimeng Cai Md. Abdul Masum Osamu Ichii Kensuke Takada Mutsumi Inaba |
author_sort |
Shangyi Wang |
title |
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model |
title_short |
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model |
title_full |
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model |
title_fullStr |
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model |
title_full_unstemmed |
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model |
title_sort |
rev-erb agonist suppresses il-17 production in γδt cells and improves psoriatic dermatitis in a mouse model |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-12-01 |
description |
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 γδT 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 γδT (γδT17) cells remains unclear. Here we revealed the regulatory mechanism involving γδT17 cells through REV-ERBs. γδT17 cell levels were remarkably elevated in the secondary lymphoid organs of mice that lacked an isoform of REV-ERBs. A synthetic REV-ERB agonist, SR9009, suppressed γδT17 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 γδT17 cells. |
topic |
IL-17 γδT cells Psoriasis Nuclear receptor REV-ERB |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221010672 |
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