The role of interleukin-17 in the pathogenesis of systemic sclerosis: Pro-fibrotic or anti-fibrotic?

J Scleroderma Relat Disord. 2021 Oct;6(3):227-235. doi: 10.1177/23971983211039421. Epub 2021 Aug 14.

Abstract

Systemic sclerosis is characterized by widespread fibrosis of the skin and internal organs, vascular impairment, and dysregulation of innate and adaptive immune system. Growing evidence indicates that T-cell proliferation and cytokine secretion play a major role in the initiation of systemic sclerosis, but the role of T helper 17 cells and of interleukin-17 cytokines in the development and progression of the disease remains controversial. In particular, an equally distributed body of literature supports both pro-fibrotic and anti-fibrotic effects of interleukin-17, suggesting a complex and nuanced role of this cytokine in systemic sclerosis pathogenesis that may vary depending on disease stage, target cells in affected organs, and inflammatory milieu. Although interleukin-17 already represents an established therapeutic target for several immune-mediated inflammatory diseases, more robust experimental evidence is required to clarify whether it may become an attractive therapeutic target for systemic sclerosis as well.

Keywords: Systemic sclerosis; T helper 17; fibroblast; fibrosis; interleukin-17.

Publication types

  • Review