Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses
Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses
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DOI：
10.1002/eji.201546263
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发表时间：
2016-08-01
影响因子：
5.4
通讯作者：
Saalbach, Anja
中科院分区：
文献类型：
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作者：
Stelzner, Kristin;Herbert, Diana;Saalbach, Anja
肥胖与身体脂肪增加和葡萄糖代谢受损有关。在这里，我们确定肥胖的体脂增加和糖代谢受损是血清游离脂肪酸(FFAs)水平升高的两个独立危险因素。由于肥胖与银屑病等各种慢性炎症性疾病中观察到的炎症消退增加和/或延迟有关，我们研究了游离脂肪酸对人单核细胞来源的树突状细胞(DC)和小鼠骨髓来源的树突状细胞(DC)功能的影响，这些树突状细胞与慢性炎症的发病机制有关。棕榈酸(PA)和油酸(OA)等游离脂肪酸不影响DC的促炎免疫反应。相反，PA和OA使DC敏化，导致促炎刺激时TH1/TH17指导性细胞因子的分泌增加。有趣的是，小鼠的肥胖加重了由TH1/TH17驱动的牛皮癣样皮肤炎症。血清中总FFA、PA和OA的含量与皮肤炎症的严重程度之间的强烈相关性表明，FFA在肥胖介导的皮肤炎症加剧中起着关键作用。我们的数据表明，FFAs水平的增加可能是促进TH1/TH17介导的炎症(如银屑病)的一个易感因素，以响应炎症危险信号。
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.