Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis

Ai Kuzumi, Ayumi Yoshizaki, Kazuki M. Matsuda, Hirohito Kotani, Yuta Norimatsu, Maiko Fukayama, Satoshi Ebata, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Yoshihide Asano, Kyojiro Morikawa, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

Original languageEnglish
Article number5947
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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