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  2. 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

  • Front Immunol. 2020 Feb 18;11:250. doi: 10.3389/fimmu.2020.00250.
Yuhui Miao 1 2 3 4 Ming Jiang 1 2 3 4 Lu Qi 1 2 3 4 De Yang 5 Weihua Xiao 1 2 3 4 Fang Fang 1 2 3 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Institute of Immunology, University of Science and Technology of China, Hefei, China.
  • 4 Engineering Technology Research Center of Biotechnology Drugs Anhui, University of Science and Technology of China, Hefei, China.
  • 5 Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States.
Abstract

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-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.

Keywords

BCAP; Listeria monocytogenes; NF-κB signaling; PI3K/AKT signaling; Toll-like receptors; dendritic cells.

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