Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Front Immunol. 2020 Feb 18;11:250. doi: 10.3389/fimmu.2020.00250. eCollection 2020.
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 -infection model. Furthermore, we demonstrate that BCAP simultaneously modulates the activation of the NF-κB and PI3K/AKT signaling by dynamically interacting with, respectively, MyD88 and the p85α subunit of PI3K. Our study thus reveals non-redundant roles for BCAP in regulating cDC maturation and reveals a bilateral signal transduction mechanism.
树突状细胞（DCs）的成熟对于适应性免疫至关重要。B 细胞衔接蛋白对于磷酸肌醇 3-激酶（BCAP）的作用在不同细胞类型中表现出不同的活性，包括 B 细胞、NK 细胞、巨噬细胞和浆细胞样 DCs（pDCs），然而，其在常规 DCs（cDCs）中的作用尚不清楚。在这里，我们报告称，BCAP 负调控 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，从而削弱了感染模型中小鼠的抗菌适应性免疫反应。此外，我们证明 BCAP 分别通过与 MyD88 和 PI3K 的 p85α亚基动态相互作用，同时调节 NF-κB 和 PI3K/AKT 信号的激活。因此，我们的研究揭示了 BCAP 在调节 cDC 成熟中的非冗余作用，并揭示了一种双向信号转导机制。
