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The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets

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Abstract

Skin fibrosis, characterized by excessive fibroblast proliferation and extracellular matrix deposition in the dermis, is the histopathologic hallmark of dermatologic diseases such as systemic sclerosis, hypertrophic scars, and keloids. Effective anti-scarring therapeutics remain an unmet need, underscoring the complex pathophysiologic mechanisms of skin fibrosis. The Th2 cytokines interleukin (IL)-4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders. The goal of this article is to summarize the current understanding of the role of the IL-4/IL-13 axis in wound healing and skin fibrosis. We conducted a literature search to identify research studies investigating the roles of IL-4 and IL-13 in fibrotic skin diseases. While transforming growth factor-beta has long been regarded as the main driver of fibrotic processes, research into the cellular and molecular biology of wound healing has revealed other pathways that promote scar tissue formation. IL-4 and IL-13 are important mediators of skin fibrosis, supported by evidence from in vitro data, animal models of fibrosis, and clinical studies. Overactive signaling of the IL-4/IL-13 axis contributes to the initiation and perpetuation of fibrotic skin diseases. Further insights into the IL-4/IL-13 axis may reveal potential targets for the development of novel therapies that prevent or treat fibrotic skin diseases.

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Funding

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award no. K23GM117309.

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  1. Evan Austin and Alisen Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, SUNY Downstate Medical Center, 450 Clarkson Avenue MSC 46, Brooklyn, NY, 11203, USA

    Julie K. Nguyen, Evan Austin, Alisen Huang, Andrew Mamalis & Jared Jagdeo

  2. Dermatology Service, VA New York Harbor Healthcare System, Brooklyn, NY, USA

    Jared Jagdeo

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  1. Julie K. Nguyen
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  2. Evan Austin
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Nguyen, J.K., Austin, E., Huang, A. et al. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res 312, 81–92 (2020). https://doi.org/10.1007/s00403-019-01972-3

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