| First Author | Acharya M | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 7 | Pages | 1810-1818 |
| PubMed ID | 32859730 | Mgi Jnum | J:301520 |
| Mgi Id | MGI:6502441 | Doi | 10.4049/jimmunol.1901056 |
| Citation | Acharya M, et al. (2020) B Cell alphav Integrins Regulate TLR-Driven Autoimmunity. J Immunol 205(7):1810-1818 |
| abstractText | Systemic lupus erythematosus (SLE) is defined by loss of B cell tolerance, resulting in production of autoantibodies against nucleic acids and other cellular Ags. Aberrant activation of TLRs by self-derived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism by which TLR signaling to self-ligands is regulated remains poorly understood. In this study, we show that alphav integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of alphav from B cells accelerates autoantibody production and autoimmune kidney disease in the Tlr7.1 transgenic mouse model of SLE. Increased autoimmunity was associated with specific expansion of transitional B cells, extrafollicular IgG2c-producing plasma cells, and activation of CD4 and CD8 T cells. Our data show that alphav-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of alphav promotes escape from tolerance. Thus, we identify a new regulatory pathway in autoimmunity and elucidate upstream signals that adjust B cell activation to prevent development of autoimmunity in a mouse model. |
