title: Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses.
abstract: Obesity is associated with body fat gain and impaired glucose metabolism. Here, we identified both body fat gain in obesity and impaired glucose metabolism as two independent risk factors for increased serum levels of free fatty acids (FFAs). Since obesity is associated with increased and/or delayed resolution of inflammation observed in various chronic inflammatory diseases such as psoriasis, we investigated the impact of FFAs on human monocyte-derived and mouse bone marrow-derived dendritic cell (DCs) functions relevant for the pathogenesis of chronic inflammation. FFAs such as palmitic acid (PA) and oleic acid (OA) did not affect the pro-inflammatory immune response of DCs. In contrast, PA and OA sensitize DCs resulting in augmented secretion of TH1/TH17-instructive cytokines upon pro-inflammatory stimulation. Interestingly, obesity in mice worsened a TH1/TH17-driven psoriasis-like skin inflammation. Strong correlation of the amount of total FFA, PA, and OA in serum with the severity of skin inflammation points to a critical role of FFA in obesity-mediated exacerbation of skin inflammation. Our data suggest that increased levels of FFAs might be a predisposing factor promoting a TH1/TH17-mediated inflammation such as psoriasis in response to an inflammatory danger signal.
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Stelzner
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Herbert
authors.affiliation: Institute of Medical Physics and Biophysics, Medical Faculty of University of Leipzig, Germany.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Popkova
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Lorz
authors.affiliation: Institute of Medical Physics and Biophysics, Medical Faculty of University of Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.affiliation: Institute of Anatomy, Medical Faculty of University of Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.affiliation: Department of Medicine, Medical Faculty of University of Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franz
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Saalbach
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators
keywords: Dendritic cells; Diet; Free fatty acids; Inflammation; Metabolism; TH1; TH17