BCAP Regulates Dendritic Cell Maturation Through the Dual-Regulation of NF-κB and PI3K/AKT Signaling During Infection
BCAP Regulates Dendritic Cell Maturation Through the Dual-Regulation of NF-κB and PI3K/AKT Signaling During Infection
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BCAP 在感染过程中通过 NF-kappa B 和 PI3K/AKT 信号传导的双重调节来调节树突状细胞成熟
DOI：
10.3389/fimmu.2020.00250
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发表时间：
2020-02-18
影响因子：
7.3
通讯作者：
Fang, Fang
中科院分区：
文献类型：
--
作者：
Miao, Yuhui;Jiang, Ming;Fang, Fang
树突状细胞(DC)的成熟在获得性免疫中是必不可少的。肌醇磷脂3-激酶(BCAP)的B细胞适配蛋白(BCAP)在B细胞、NK细胞、巨噬细胞和浆细胞样树突状细胞(DC)中具有不同的活性，但其在传统DC(CDCs)中的作用尚不清楚。在此，我们报道了BCAP负性调节Toll样受体诱导的CDC成熟，并抑制CDC诱导抗原特异性T细胞反应，从而在单核细胞增多性李斯特菌感染模型中削弱小鼠的抗细菌获得性免疫反应。此外，我们还证明了BCAP通过分别与PI3K的MyD88和P85α亚基动态地相互作用，同时调节了NF-kappa B和PI3K/AKT信号的激活。因此，我们的研究揭示了BCAP在调节CDC成熟过程中的非多余作用，并揭示了一种双边信号转导机制。
The maturation of dendritic cells (DCs) is essential in adaptive immunity. B cell adapter for phosphoinositide 3-kinase (BCAP) has been shown a divergent activities in cell type dependent manner including B cells, NK cells, macrophages, and plasmacytoid DCs (pDCs), however, its role in conventional DCs (cDCs) remains unknown. Here, we report that BCAP negatively regulates Toll-like receptor-induced cDC maturation and inhibits cDCs from inducing antigen-specific T cell responses, thereby weakening the antibacterial adaptive immune responses of mice in a Listeria monocytogenes-infection model. Furthermore, we demonstrate that BCAP simultaneously modulates the activation of the NF-kappa B and PI3K/AKT signaling by dynamically interacting with, respectively, MyD88 and the p85 alpha subunit of PI3K. Our study thus reveals non-redundant roles for BCAP in regulating cDC maturation and reveals a bilateral signal transduction mechanism.