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Immunopathobiology and therapeutic targets related to cytokines in liver diseases

Cellular & Molecular Immunology volume 18, pages 18–37 (2021)Cite this article

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Abstract

Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma. The progression of liver disease is controlled by a variety of factors, including liver injury, inflammatory cells, inflammatory mediators, cytokines, and the gut microbiome. In the current review, we discuss recent data on a large number of cytokines that play important roles in regulating liver injury, inflammation, fibrosis, and regeneration, with a focus on interferons and T helper (Th) 1, Th2, Th9, Th17, interleukin (IL)-1 family, IL-6 family, and IL-20 family cytokines. Hepatocytes can also produce certain cytokines (such as IL-7, IL-11, and IL-33), and the functions of these cytokines in the liver are briefly summarized. Several cytokines have great therapeutic potential, and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases, which are also described.

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Acknowledgements

The current review covers a very broad topic, and the authors apologize to the colleagues whose work was not mentioned or cited in this paper because of space constraints and the limited number of references that are allowed. The work from the authors’ laboratories described in this review article was supported by the intramural program of the NIAAA (Bin Gao), U01 AA022614, and R01 DK099205 (Tatiana Kisseleva) and AA011576 and AA017729 (Gyongyi Szabo).

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Author notes

  1. These authors contributed equally: Yong He, Seonghwan Hwang

Authors and Affiliations

  1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA

    Yong He, Seonghwan Hwang, Yeni Ait Ahmed, Dechun Feng & Bin Gao

  2. Université Paris-Est, UMR-S955, UPEC, F-94000, Créteil, France

    Yeni Ait Ahmed & Fouad Lafdil

  3. Department of Medicine and Department of Surgery, School of Medicine, University of California, San Diego, CA, 92093, USA

    Na Li & Tatiana Kisseleva

  4. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Marcelle Ribeiro & Gyongyi Szabo

  5. INSERM, U955, F-94000, Créteil, France

    Fouad Lafdil

  6. Institut Universitaire de France (IUF), Paris, F-75231, Cedex 05, France

    Fouad Lafdil

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  1. Yong He
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Contributions

Y.H. and S.H. share first authorship. Y.H. wrote the sections on Th1 and IL-20 family cytokines and hepatocyte-derived cytokines; S.H. wrote the sections on Th2 and Th9 cytokines; Y.A.A. and F.L. wrote the section on IL-6 family cytokines; D.F. wrote the section on IL-22 cytokine; N.L. and T.K. wrote the section on IL-17 family cytokines; M.R. and G.S. wrote the section on IL-1 family cytokines; and B.G. initiated and supervised the paper writing process and edited the paper. Y.A.A. was a participant in the NIH Graduate Partnerships Program and a graduate student at the Université Paris-Est, France and is affiliated with the Université Paris-Est and the NIH Graduate Partnerships Program.

Corresponding author

Correspondence to Bin Gao.

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Competing interests

G.S. consults for Allergan, Alnylam, Arrow, Durcect Corporation, Generon, Glympse Bio, Terra Firma, Quest Diagnostics, Pandion Therapeutics, Surrozen, and Zomagen. She has received grants from Gilead, Genfit, Intercept, Novartis, SignaBlok, and Shire. She holds intellectual property rights with Up to Date. The other coauthors declare no competing interests.

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He, Y., Hwang, S., Ahmed, Y.A. et al. Immunopathobiology and therapeutic targets related to cytokines in liver diseases. Cell Mol Immunol 18, 18–37 (2021). https://doi.org/10.1038/s41423-020-00580-w

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