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Interleukin-33 in the pathogenesis of liver fibrosis: alarming ILC2 and hepatic stellate cells

Cellular & Molecular Immunology volume 14, pages 143–145 (2017)Cite this article

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Interleukin-33 (IL-33), a cytokine of the IL-1 family, has been implicated in the pathogenesis of liver fibrosis for quite some time. Indeed, IL-33 expression is upregulated in both human and murine hepatic fibrosis.1, 2 To date, it is believed that IL-33 serves as an ‘alarmin’ released by stressed hepatocytes. IL-33 then attracts type 2 innate lymphoid cells (ILC), which trigger the profibrogenic activation of hepatic stellate cells via mediators such as IL-13.1, 3 IL-33 signals through a unique IL-1 receptor-related protein that is termed suppressor of tumorigenicity 2 (ST2), also called IL-33R. The binding of IL-33 to ST2 activates nuclear factor-κB and mitogen-activated protein kinases (MAPKs) and drives the production of pro-inflammatory and T helper type 2 (Th2)-associated cytokines.4

The relationship between inflammation and IL-33 was further underpinned by the finding that intraperitoneal injections of recombinant IL-33 increased hepatic inflammation in both naive and BDL-injured livers when given 3 days prior to the BDL surgery. However, IL-33 alone failed to enhance the inflammatory response in sham-operated mice, suggesting that IL-33 has the capacity to increase the production of inflammatory cytokines only in injured livers.5 In accordance with this role, recombinant IL-33 aggravated hepatic fibrosis in experimental steatohepatitis, but had beneficial effects on hepatic steatosis.7

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Acknowledgements

Both authors are supported by the German Research Foundation (SFB/TRR 57) and the Interdisciplinary Centre for Clinical Research (IZKF) within the Faculty of Medicine at the RWTH Aachen University. The authors thank Sabine Weiskirchen for preparing the figure.

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  1. Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital RWTH Aachen, Aachen, D-52074, Germany.

    Ralf Weiskirchen

  2. Department of Medicine III, University Hospital RWTH Aachen, Aachen, D-52074, Germany.

    Frank Tacke

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  1. Ralf Weiskirchen
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  2. Frank Tacke
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Correspondence to Ralf Weiskirchen or Frank Tacke.

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Weiskirchen, R., Tacke, F. Interleukin-33 in the pathogenesis of liver fibrosis: alarming ILC2 and hepatic stellate cells. Cell Mol Immunol 14, 143–145 (2017). https://doi.org/10.1038/cmi.2016.62

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