IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells

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

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), have been implicated in the pathogenesis of various skin disorders. Previous findings showed that IL-36γ promoted wound healing in mice; however, the pathogenic role of IL-36Ra in wound healing remains unclear. We elucidated the role of IL-36Ra, a regulator of IL-36 in tissue repair by investigating the recruitment of inflammatory cells and cytokine production in the absence of IL-36Ra. Full-thickness excisional wounds were made on the back of Il36rn−/− mice and healing was assessed by monitoring macroscopic wound sizes, numbers of infiltrated cells, and gene expression of inflammatory cytokines. Macroscopic wound healing, re-epithelialization, and granulation tissue formation were delayed by 3 days post-injury in Il36rn−/− mice. This delay was associated with increased infiltrations of neutrophils and macrophages, and increased expression of cytokines, such as IL-36γ, C-X-C motif chemokine ligand 1 (CXCL1), and transforming growth factor (TGF)-β. Importantly, administration of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, caused normalization of wound healing in Il36rn−/− mice, abrogating the initial delay in tissue repair. These results showed that targeting TLR4- mediated infiltrations of immune cells and cytokine production could be beneficial in regulating wound healing in IL-36Ra-deficient skin disorders.

本文言語English
論文番号14772
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 01-12-2020

All Science Journal Classification (ASJC) codes

  • 一般

フィンガープリント

「IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル