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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Main Authors: Shangyi Wang, Mina Kozai, Hironobu Mita, Zimeng Cai, Md. Abdul Masum, Osamu Ichii, Kensuke Takada, Mutsumi Inaba
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332221010672
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spelling 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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