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- Title
Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis.
- Authors
Kuzumi, Ai; Yoshizaki, Ayumi; Matsuda, Kazuki M.; Kotani, Hirohito; Norimatsu, Yuta; Fukayama, Maiko; Ebata, Satoshi; Fukasawa, Takemichi; Yoshizaki-Ogawa, Asako; Asano, Yoshihide; Morikawa, Kyojiro; Kazoe, Yutaka; Mawatari, Kazuma; Kitamori, Takehiko; Sato, Shinichi
- 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. Systemic sclerosis (SSc) disease involves multisystem fibrosis and autoimmunity with limited treatment options. Here the authors demonstrate that IL-31 and IL-31RA are overexpressed in dermal fibroblasts from SSc patients and show that fibrosis and cytokine release can be reduced upon blocking of IL-31/IL-31RA.
- Subjects
SYSTEMIC scleroderma; FIBROSIS; LABORATORY mice; FIBROBLASTS; CYTOKINES
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-26099-w