title: High-Fat Diet-Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vasseur
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Serres
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jégou
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Pohin
authors.affiliation: ImageUP, CNRS ERL 7368, Poitiers University, Poitiers, France; STIM Laboratory, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Delwail
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit-Paris
authors.affiliation: Department of Pathology, Poitiers University Hospital, Poitiers, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Levillain
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Favot
authors.affiliation: IRSET, Inserm U1085, University of Rennes 1, Rennes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, CIMI, Inserm U1135, Paris, France.
authors.forename: Hans
authors.initials: H
authors.lastname: Yssel
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morel
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Silvain
authors.affiliation: Laboratory of Inflammation and Epithelial and Cytokine Tissues EA 4331, CNRS ERL 7368, Poitiers University, Poitiers, France; Department of Immunology/Inflammation, Poitiers University Hospital, Poitiers, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000150:complications / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17