Histone Deacetylase Inhibitors Attenuate Hepatic Fibrosis through Suppression of Group 2 Innate Lymphoid Cells and Type 2 Inflammation

Le résumé fourni par la source

Deposition of collagen and matrix proteins is essential for tissue repair and remodelling. Chronic liver diseases typically show excessive matrix protein deposition or crosslinking that leads to scar tissue, obstructs blood flow and disrupts liver functions, all characteristics of advanced liver damage in cirrhosis. There are no effective anti‐fibrotic therapies. Immunomodulatory mechanisms that contribute to fibrogenesis in chronic liver disease are not fully elucidated. Here we examine thioacetamide‐induced liver injury in mice, which develop progressive hepatic inflammation and fibrosis similar to clinical features of chronic human liver disease. We find that inhibitors of class I, but not class II, histone deacetylase (HDAC) enzymes suppress hepatic inflammation and fibrosis in this model. Inhibitors of class I HDACs attenuate accumulation and activation of group 2 innate lymphoid cells (ILC2), specifically interleukin (IL)‐33 (but not IL‐25) dependent CD45 + /Lin −/ Thy‐1 + /ST2 + /KLRG1 int ILC2 cells, associated with type 2 inflammation that drives hepatic stellate cells to secrete excessive matrix proteins. Some HDAC inhibitors that are registered anti‐cancer drugs might be repurposed for treating chronic liver fibrosis. Support or Funding Information ZL acknowledges salary support from the Centre for Inflammation and Disease Research, University of Queensland. The National Health and Medical Research Council of Australia is acknowledged for a Career Development Fellowship to KS (1141131), a Senior Research Fellowship to MJS (1107914) and a Senior Principal Research Fellowship to DPF (1117017). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

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