High-Fat Diet–Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis

• Published in: The American journal of pathology Vol. 186; no. 9; pp. 2292 - 2301
• Main Authors: Vasseur, Philippe, Serres, Laure, Jégou, Jean-François, Pohin, Mathilde, Delwail, Adriana, Petit-Paris, Isabelle, Levillain, Pierre, Favot, Laure, Samson, Michel, Yssel, Hans, Morel, Franck, Silvain, Christine, Lecron, Jean-Claude
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016; American Society for Investigative Pathology / Elsevier
• Subjects: Animals; Dermatitis - complications; Dermatitis - pathology; Diet, High-Fat - adverse effects; Disease Models, Animal; Ecology, environment; Flow Cytometry; Fluorescent Antibody Technique; Health; Interleukin-17 - metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - pathology; Pathology; Real-Time Polymerase Chain Reaction; liver-disease; il-22; risk; cytokines; innate lymphoid-cells; mice; skin inflammation
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2016.05.012

Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermal infiltrates of CD45+ leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1β. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet–induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients.