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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.

Original publication

DOI

10.1016/j.ajpath.2016.05.012

Type

Journal article

Journal

The american journal of pathology

Publication Date

09/2016

Volume

186

Pages

2292 - 2301

Addresses

Department of Hepatogastroenterology, Poitiers University Hospital, Poitiers, France; Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France. Electronic address: vasseur.philippe@chnds.fr.

Keywords

Animals, Mice, Inbred C57BL, Mice, Dermatitis, Disease Models, Animal, Interleukin-17, Fluorescent Antibody Technique, Flow Cytometry, Male, Real-Time Polymerase Chain Reaction, Diet, High-Fat, Non-alcoholic Fatty Liver Disease