Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35-55-immunized FABP(-/-) mice showed reduced proliferation and impaired IFN-gamma production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP(-/-) dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.

译文

:脂肪酸结合蛋白(FABP)充当多种疏水化合物的细胞内受体,使其在细胞质区室中扩散。最近的研究表明FABP同时调节代谢和炎症途径的能力。我们调查了脂肪细胞FABP和上皮FABP在实验性自身免疫性脑脊髓炎的发展中的作用,以检验以下假设:这些FABP影响适应性免疫反应并有助于自身免疫性疾病的发病机理。与野生型小鼠相比,FABP缺陷型小鼠表现出较低的疾病发病率,减少了实验性自身免疫性脑脊髓炎的临床症状,并且在CNS组织中的促炎细胞因子mRNA表达水平大大降低。髓鞘少突胶质细胞糖蛋白35-55免疫的FABP(-/-)小鼠的体外Ag召回反应显示出增殖减少和IFN-γ产生受损。发现缺乏FABP的树突状细胞是促炎性细胞因子的不良生产者,并且FABP(-/-)树突状细胞的Ag呈递并不促进促炎性T细胞应答。这项研究表明,FABPs对代谢-炎症途径的交叉调节有助于适应性免疫反应和随后的自身免疫炎症。

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