Free fatty acids sensitize dendritic cells to amplify TH1/TH17‐immune responses |
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Authors: | Kristin Stelzner Diana Herbert Yulia Popkova Axel Lorz Jürgen Schiller Martin Gericke Nora Klöting Matthias Blüher Sandra Franz Jan C Simon Anja Saalbach |
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Institution: | 1. Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Germany;2. Institute of Medical Physics and Biophysics, Medical Faculty of University of Leipzig, Germany;3. Institute of Anatomy, Medical Faculty of University of Leipzig, Germany;4. IFB Adiposity Diseases, University of Leipzig, Germany;5. Department of Medicine, Medical Faculty of University of Leipzig, Germany |
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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. |
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Keywords: | Dendritic cells Diet Free fatty acids Inflammation Metabolism TH1 TH17 |
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