Blimp-1-Mediated Pathway Promotes Type I IFN Production in Plasmacytoid Dendritic Cells by Targeting to Interleukin-1 Receptor-Associated Kinase M.

摘要: Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs capable rapidly producing copious amounts type I IFN (IFN-I) in response to viral infections. The mechanism regulating rapid production IFN-I after pDCs exposed nucleic acids remains elusive. Here, we show that the transcription factor Blimp-1 is promptly induced exposure TLR7 and TLR9 ligands via unique Ras-related C3 botulinum toxin substrate (Rac)-mediated pathway. Deletion Prdm1 gene encoding impaired IFN-I, but not other cytokines, upon infection or treatment with CpG DNA pDCs. Accordingly, mice lacking failed produce stimulation did mount proper antiviral responses following flavivirus infection. development bone marrow as well induction several activation markers, such CD86, CD69, MHCII, by was generally affected absence Blimp-1. Mechanistically, found controls IKKα IRF7 directly suppressing interleukin-1 receptor-associated kinase 3 (Irak3), negative regulator TLR signaling, Together, identify Blimp-1-dependent pathway facilitates relieving M, encoded Irak3,