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Review
. 2024 Oct 22:11:1470362.
doi: 10.3389/fcvm.2024.1470362. eCollection 2024.

The role of IL-17 family cytokines in cardiac fibrosis

Liqing Huang  1
Affiliations
Review

The role of IL-17 family cytokines in cardiac fibrosis

Liqing Huang. Front Cardiovasc Med. .

Abstract

Myocardial fibrosis is a common pathological feature in various cardiovascular diseases including myocardial infarction, heart failure, and myocarditis. Generally, persistent myocardial fibrosis correlates with poor prognosis and ranks among the leading causes of death globally. Currently, there is no effective treatment for myocardial fibrosis, partly due to its unclear pathogenic mechanism. Increasing studies have shown IL-17 family cytokines are strongly associated with the initiation and propagation of myocardial fibrosis. This review summarizes the expression, action, and signal transduction mechanisms of IL-17, focusing on its role in fibrosis associated with cardiovascular diseases such as myocardial infarction, heart failure, hypertension, diabetes, and myocarditis. It also discusses its potential as a therapeutic target, offering new insights for the clinical treatment of myocardial fibrosis.

Keywords: IL-17; cardiac fibrosis; extracellular matrix; fibroblast; myofibroblast.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pathophysiologic roles of IL-17 signaling in cardiac fibrosis. The IL-17 family cytokines include IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. The IL-17A/IL-17F mediated signaling pathway has been extensively studied. After IL-17A/IL-17F binds to the IL17RA/RC receptor complex, the receptor complex recruits the signal transduction adaptor protein Act1 through its SEFIR domain.Act1 serves as the crucial molecule for all known downstream signaling pathways of IL-17A. Act1 rapidly recruits and ubiquitinates TRAF6, activating various downstream pathways, including: the TRAF6/TAK1/NF-κB pathway, TRAF6/MAPK/AP-1 pathway, and Act1/TRAF6/CREB pathway, which induce transcription of IL-17A target genes. Furthermore, Act1 promotes mRNA stabilization post-transcription by recruiting TRAF2 and TRAF5. Ultimately, IL-17 induces the expression of pro-inflammatory and pro-fibrosis molecules and stimulate activation, proliferation, migration, and secretion of myocardial fibroblasts, thereby aggravating cardial fibrosis. Adapted with permission from “Cell Types”, by BioRender.com (2024), licensed under Academic License. Created in BioRender. T4, V. (2022).
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The author declares that no financial support was received for the research, authorship, and/or publication of this article.

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