Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis
| Autor: | Kyojiro Morikawa, Kazuki M. Matsuda, Ayumi Yoshizaki, Takehiko Kitamori, Ai Kuzumi, Yuta Norimatsu, Maiko Fukayama, Yutaka Kazoe, Asako Yoshizaki-Ogawa, Yoshihide Asano, Takemichi Fukasawa, Shinichi Sato, Hirohito Kotani, Kazuma Mawatari, Satoshi Ebata |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
General Physics and Astronomy Autoimmunity medicine.disease_cause T-Lymphocytes Regulatory Scleroderma Pathogenesis Mice Fibrosis Medicine Protein Isoforms skin and connective tissue diseases Skin Multidisciplinary Interleukin-13 biology integumentary system Interleukin Antibodies Monoclonal Middle Aged STAT1 Transcription Factor Female Antibody Adult Science T-helper 2 cells General Biochemistry Genetics and Molecular Biology Collagen Type I Article Immune system Th2 Cells Rheumatology Animals Humans Aged Scleroderma Systemic business.industry Interleukin-6 Interleukins General Chemistry Receptors Interleukin Fibroblasts medicine.disease Collagen Type I alpha 1 Chain Disease Models Animal Interleukin 31 Gene Expression Regulation Immunology biology.protein Interleukin-4 business |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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