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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 5947 (10 12 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34642338 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Monoclonal
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• IL13 protein, human
• IL31 protein, human
• IL31RA protein, human
• IL4 protein, human
• IL6 protein, human
• Interleukin-13
• Interleukin-6
• Interleukins
• Protein Isoforms
• Receptors, Interleukin
• STAT1 Transcription Factor
• STAT1 protein, human
• Interleukin-4

Topics

• Adult
• Aged
• Animals
• Antibodies, Monoclonal (pharmacology)
• Collagen Type I (genetics, immunology)
• Collagen Type I, alpha 1 Chain
• Disease Models, Animal
• Female
• Fibroblasts (drug effects, immunology, pathology)
• Fibrosis
• Gene Expression Regulation
• Humans
• Interleukin-13 (genetics, immunology)
• Interleukin-4 (genetics, immunology)
• Interleukin-6 (genetics, immunology)
• Interleukins (genetics, immunology)
• Male
• Mice
• Middle Aged
• Protein Isoforms (genetics, immunology)
• Receptors, Interleukin (antagonists & inhibitors, genetics, immunology)
• STAT1 Transcription Factor (genetics, immunology)
• Scleroderma, Systemic (drug therapy, genetics, immunology, pathology)
• Skin (drug effects, immunology, pathology)
• T-Lymphocytes, Regulatory (drug effects, immunology, pathology)
• Th2 Cells (drug effects, immunology, pathology)