TAK-242 ameliorates contact dermatitis exacerbated by IL-36 receptor antagonist deficiency

Hidehiko Fukushima, Yohei Iwata, Soichiro Watanabe, Kenta Saito, Yoshihito Tanaka, Yurie Hasegawa, Masashi Akiyama, Kazumitsu Sugiura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Loss-of-function mutations in IL36RN cause generalized pustular psoriasis (GPP), which is characterized by neutrophil-infiltrated lesions. Neutrophils are important during contact hypersensitivity in mice. However, it has never been determined whether interleukin-36 receptor antagonist (IL-36Ra) deficiency is an exacerbating factor in contact dermatitis. We examined whether a loss-of-function IL36RN mutation exacerbates contact dermatitis and evaluated the changes in contact dermatitis-related cytokines. Wild-type and Il36rn−/− mice were treated with 1-fluoro-2,4-dinitorobenzene (DNFB) and evaluated for ear thickness, histopathological features, numbers of infiltrated neutrophils, and numbers of CD4 + and CD8 + T cells. Furthermore, mRNA levels of contact dermatitis-related cytokines were measured by real-time polymerase chain reaction, and effects of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, on the contact hypersensitivity (CHS) response were evaluated. We found that the ear thickness, cytokine expression, and neutrophil infiltration significantly increased in Il36rn−/− mice compared with that in wild-type mice. TAK-242 alleviated CHS and prevented neutrophil infiltration, cytokine expression, and ear thickening in Il36rn−/− mice. These data indicate that Il36rn−/− mutations are an exacerbating factor for CHS and that TAK-242 can reduce the inflammatory responses that are associated with the CHS response.

Original languageEnglish
Article number734
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - 01-12-2020

All Science Journal Classification (ASJC) codes

  • General

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