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

Author

Listed:
  • Ai Kuzumi

    (The University of Tokyo)

  • Ayumi Yoshizaki

    (The University of Tokyo)

  • Kazuki M. Matsuda

    (The University of Tokyo)

  • Hirohito Kotani

    (The University of Tokyo)

  • Yuta Norimatsu

    (The University of Tokyo)

  • Maiko Fukayama

    (The University of Tokyo)

  • Satoshi Ebata

    (The University of Tokyo)

  • Takemichi Fukasawa

    (The University of Tokyo)

  • Asako Yoshizaki-Ogawa

    (The University of Tokyo)

  • Yoshihide Asano

    (The University of Tokyo)

  • Kyojiro Morikawa

    (The University of Tokyo)

  • Yutaka Kazoe

    (Faculty of Science and Technology, Keio University)

  • Kazuma Mawatari

    (The University of Tokyo)

  • Takehiko Kitamori

    (The University of Tokyo)

  • Shinichi Sato

    (The University of Tokyo)

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.

Suggested Citation

  • Ai Kuzumi & Ayumi Yoshizaki & Kazuki M. Matsuda & Hirohito Kotani & Yuta Norimatsu & Maiko Fukayama & Satoshi Ebata & Takemichi Fukasawa & Asako Yoshizaki-Ogawa & Yoshihide Asano & Kyojiro Morikawa & , 2021. "Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26099-w
    DOI: 10.1038/s41467-021-26099-w
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    Cited by:

    1. Santhoshi V. Akkenepally & Dan J. K. Yombo & Sanjana Yerubandi & Geereddy Bhanuprakash Reddy & Deepak A. Deshpande & Francis X. McCormack & Satish K. Madala, 2023. "Interleukin 31 receptor α promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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