Endogenous IL-33 has no effect on the progression of fibrosis during experimental steatohepatitis

Philippe Vasseur (1) , Sarah Dion (2) , Aveline Filliol (2) , Valentine Genet (2) , Catherine Lucas-Clerc (3) , Jean-Philippe Girard (4) , Christine Silvain (5, 1) , Jean-Claude Lecron (1) , Claire Piquet-Pellorce (2) , Michel Samson (2)

1 LITEC [Poitiers] - Laboratoire Inflammation, Tissus épithéliaux et Cytokines [EA 4331]
2 Irset - Institut de recherche en santé, environnement et travail
3 Laboratoire de biochimie générale
4 IPBS - Institut de pharmacologie et de biologie structurale
5 Hôpital de la Milétrie

Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL33-/-HFD mice than in WT-HFD mice. Nevertheless, IL-33 deficiency did not affect the severity of liver inflammation by histological and transcriptomic analyses, nor the quantity of liver fibrosis. Livers from HFD mice had more myeloid populations, markedly fewer NKT cells and higher proportion of ST2+ Treg cells and ST2+ type 2 innate lymphoid cells (ILC2), all unaffected by IL-33 deficiency. In conclusion, deficiency of endogenous IL-33 does not affect the evolution of experimental diet-induced steatohepatitis towards liver fibrosis.

Mots clés: nonalcoholic steatohepatitis; nash; nonalcoholic fatty liver disease; nafld; immune cells; NASH; NAFLD

Domaines: Santé publique et épidémiologie

Philippe Vasseur, Sarah Dion, Aveline Filliol, Valentine Genet, Catherine Lucas-Clerc, et al.. Endogenous IL-33 has no effect on the progression of fibrosis during experimental steatohepatitis. Oncotarget, 2017, 8 (30), pp.48563--48574. ⟨10.18632/oncotarget.18335⟩. ⟨hal-01578584⟩