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REVIEW article

Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1437046
This article is part of the Research Topic Adaptive Immune Regulation of Non-Alcoholic Steatohepatitis (NASH) View all articles

Role of the Type 3 Cytokines IL-17 and IL-22 in Modulating Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Provisionally accepted
  • University of Montreal Hospital Centre (CRCHUM), Montreal, Quebec, Canada

The final, formatted version of the article will be published soon.

    Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases that span simple steatosis, metabolic associated steatohepatitis (MASH) and fibrosis and may progress to cirrhosis and cancer. The pathogenesis of MASLD is multifactorial and is driven by environmental, genetic, metabolic and immune factors. This review will focus on the role of the type 3 cytokines IL-17 and IL-22 in MASLD pathogenesis and progression. IL-17 and IL-22 are produced by similar adaptive and innate immune cells such as Th17 and innate lymphoid cells, respectively. IL-17-related signaling is upregulated during MASLD resulting in increased chemokines and proinflammatory cytokines in the liver microenvironment, enhanced recruitment of myeloid cells and T cells leading to exacerbation of inflammation and liver disease progression.IL-17 may also act directly by activating hepatic stellate cells resulting in increased fibrosis. In contrast, IL-22 is a pleiotropic cytokine with a dominantly protective signature in MASLD and is currently being tested as a therapeutic strategy. IL-22 also exhibits beneficial metabolic effects and abrogates MASH-related inflammation and fibrosis development via inducing the production of anti-oxidants and anti-apoptotic factors. A sex-dependent effect has been attributed to both cytokines, most importantly to IL-22 in MASLD or related conditions. Altogether, are key effectors in MASLD pathogenesis and progression. We will review the role of these two cytokines and cells that produce them in the development of MASLD, their interaction with host factors driving MASLD including sexual dimorphism and their potential therapeutic benefits.

    Keywords: Metabolic dysfunction-associated steatotic liver disease, metabolic-associated steatohepatitis, liver fibrosis, IL-17, IL-22, sexual dimorphism

    Received: 23 May 2024; Accepted: 12 Jul 2024.

    Copyright: © 2024 Abdelnabi, Hassan and Shoukry. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Naglaa H. Shoukry, University of Montreal Hospital Centre (CRCHUM), Montreal, QC H2X 0A9, Quebec, Canada

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.