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

doi:10.1038/s41467-021-26099-w

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

Department of System Design Engineering

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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 language	English
Article number	5947
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26099-w
Publication status	Published - 2021 Dec 1

ASJC Scopus subject areas

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

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Kuzumi, A., Yoshizaki, A., Matsuda, K. M., Kotani, H., Norimatsu, Y., Fukayama, M., Ebata, S., Fukasawa, T., Yoshizaki-Ogawa, A., Asano, Y., Morikawa, K., Kazoe, Y., Mawatari, K., Kitamori, T., & Sato, S. (2021). Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis. Nature communications, 12(1), Article 5947. https://doi.org/10.1038/s41467-021-26099-w

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title = "Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis",

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.",

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

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AU - Kuzumi, Ai

AU - Yoshizaki, Ayumi

AU - Matsuda, Kazuki M.

AU - Kotani, Hirohito

AU - Norimatsu, Yuta

AU - Fukayama, Maiko

AU - Ebata, Satoshi

AU - Fukasawa, Takemichi

AU - Yoshizaki-Ogawa, Asako

AU - Asano, Yoshihide

AU - Morikawa, Kyojiro

AU - Kazoe, Yutaka

AU - Mawatari, Kazuma

AU - Kitamori, Takehiko

AU - Sato, Shinichi

PY - 2021/12/1

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N2 - 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.

AB - 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.

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

Abstract

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