Details

Autor(en) / Beteiligte

• Stelzner, Kristin
• Herbert, Diana
• Popkova, Yulia
• Lorz, Axel
• Schiller, Jürgen
• Gericke, Martin
• Klöting, Nora
• Blüher, Matthias
• Franz, Sandra
• Simon, Jan C.
• Saalbach, Anja

Titel

Free fatty acids sensitize dendritic cells to amplify TH1/TH17‐immune responses

Ist Teil von

• European journal of immunology, 2016-08, Vol.46 (8), p.2043-2053

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2016

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. Body fat gain in obesity and impaired glucose metabolism are two independent risk factors that cause an increase of serum FFAs. FFAs such as PA and OA were not able to activate DCs, the key players in linking innate and adaptive immunity, whereas they sensitized monocyte‐derived DC to a subsequent danger signal such as LPS that results in an amplification of TH1/TH17 immune responses. In parallel increase of FFAs in obesity correlates with the severity of psoriasis‐like skin inflammation in mice.