| First Author | Chu T | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 9 | Pages | 2529-2534 |
| PubMed ID | 30936294 | Mgi Jnum | J:274916 |
| Mgi Id | MGI:6296920 | Doi | 10.4049/jimmunol.1801267 |
| Citation | Chu T, et al. (2019) Cutting Edge: BCAP Promotes Lupus-like Disease and TLR-Mediated Type I IFN Induction in Plasmacytoid Dendritic Cells. J Immunol 202(9):2529-2534 |
| abstractText | Systemic lupus erythematosus severity correlates with elevated serum levels of type I IFNs, cytokines produced in large quantities by plasmacytoid dendritic cells (pDC) in response to engagement of TLR7 and TLR9 with endocytosed nucleic acids. B cell adaptor for PI3K (BCAP) promoted many aspects of TLR7-driven lupus-like disease, including Isg15 and Ifit1 expression in blood and an immature pDC phenotype associated with higher IFN production. BCAP(-/-) mice produced significantly less serum IFN-alpha than wild-type mice after injection of TLR9 agonist, and BCAP promoted TLR7 and TLR9-induced IFN-alpha production specifically in pDC. TLR-induced IFN-alpha production in pDC requires DOCK2-mediated activation of Rac1 leading to activation of IKKalpha, a mechanism we show was dependent on BCAP. BCAP(-/-) pDC had decreased actin polymerization and Rac1 activation and reduced IKKalpha phosphorylation upon TLR9 stimulation. We show a novel role for BCAP in promoting TLR-induced IFN-alpha production in pDC and in systemic lupus erythematosus pathogenesis. |
