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Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis.
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.
Affiliation
  • Kuzumi A; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Yoshizaki A; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ayuyoshi@me.com.
  • Matsuda KM; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kotani H; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Norimatsu Y; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Fukayama M; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Ebata S; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Fukasawa T; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Yoshizaki-Ogawa A; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Asano Y; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Morikawa K; Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Kazoe Y; Department of System Design Engineering, Faculty of Science and Technology, Keio University, Yokohama, Japan.
  • Mawatari K; Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Kitamori T; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Sato S; Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. satos-der@h.u-tokyo.ac.jp.
Nat Commun ; 12(1): 5947, 2021 10 12.
Article in En | MEDLINE | ID: mdl-34642338
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scleroderma, Systemic / Interleukins / Receptors, Interleukin / Th2 Cells / Fibroblasts Type of study: Prognostic_studies Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scleroderma, Systemic / Interleukins / Receptors, Interleukin / Th2 Cells / Fibroblasts Type of study: Prognostic_studies Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: