Regulation of dendritic cell function and T cell priming by the fatty acid-bindilng protein aP2
Regulation of dendritic cell function and T cell priming by the fatty acid-bindilng protein aP2
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DOI：
10.4049/jimmunol.177.11.7794
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Mackay, Charles R.
中科院分区：
文献类型：
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作者：
Rolph, Michael S.;Young, Timothy R.;Mackay, Charles R.
脂肪酸结合蛋白（FABP）家族由许多保守的细胞质蛋白组成，在细胞内脂质转运、储存和代谢中起作用。全面的白细胞基因表达数据库的检查揭示了脂肪细胞FABP aP 2在人单核细胞衍生的树突状细胞（DC）中的强表达。我们从aP 2缺陷小鼠中分离出骨髓来源的DC，并显示这些细胞中DC细胞因子（包括IL-12和TNF）的表达显著受损。在aP 2缺陷型DC中，I κ B α的降解也受损，表明通过I κ B激酶-NF-κ B途径的信号传导减少。细胞因子缺陷是选择性的，因为对Ag摄取或MHC II类、CD 40、CD 80或CD 86的表达没有影响。在MLR中，aP 2缺陷型DC刺激的T细胞增殖和细胞因子产生明显低于野生型DC。此外，用钥孔血蓝蛋白/CFA免疫的aP 2缺陷小鼠显示通过再刺激的引流淋巴结细胞产生的IFN-γ减少，表明体内DC功能的类似缺陷。类似地，用天然小鼠病原体肢脱病病毒感染aP 2缺陷小鼠导致CD 8（+）T细胞产生IFN-γ的显著降低。因此，FABP aP 2在DC功能和T细胞引发中起重要作用，并提供代谢过程和免疫应答调节之间的额外联系。
The fatty acid-binding protein (FABP) family consists of a number of conserved cytoplasmic proteins with roles in intracellular lipid transport, storage, and metabolism. Examination of a comprehensive leukocyte gene expression database revealed strong expression of the adipocyte FABP aP2 in human monocyte-derived dendritic cells (DCs). We isolated bone marrow-derived DC from aP2-deficient mice, and showed that expression of DC cytokines including IL-12 and TNF was significantly impaired in these cells. Degradation of I kappa B alpha was also impaired in aP2-deficient DCs, indicative of reduced signaling through the I kappa B kinase-NF-kappa B pathway. The cytokine defect was selective because there was no effect on Ag uptake or expression of MHC class II, CD40, CD80, or CD86. In an MLR, aP2-deficient DCs stimulated markedly lower T cell proliferation and cytokine production than did wild-type DCs. Moreover, aP2-deficient mice immunized with keyhole limpet hemocyanin/CFA showed reduced production of IFN-gamma by restimulated draining lymph node cells, suggesting a similar defect in DC function in vivo. Similarly, infection of aP2-deficient mice with the natural mouse pathogen ectromelia virus resulted in substantially lower production of IFN-gamma by CD8(+) T cells. Thus, FABP aP2 plays an important role in DC function and T cell priming, and provides an additional link between metabolic processes and the regulation of immune responses.