| First Author | Christensen SR | Year | 2005 |
| Journal | J Exp Med | Volume | 202 |
| Issue | 2 | Pages | 321-31 |
| PubMed ID | 16027240 | Mgi Jnum | J:100530 |
| Mgi Id | MGI:3588807 | Doi | 10.1084/jem.20050338 |
| Citation | Christensen SR, et al. (2005) Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J Exp Med 202(2):321-31 |
| abstractText | Systemic autoimmune disease in humans and mice is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. Autoantigens, such as double-stranded (ds) DNA and the RNA-containing Smith antigen (Sm), may be selectively targeted in systemic lupus erythematosus because of their ability to activate a putative common receptor. Toll-like receptor 9 (TLR9), a receptor for CpG DNA, has been implicated in the activation of autoreactive B cells in vitro, but its role in promoting autoantibody production and disease in vivo has not been determined. We show that in TLR9-deficient lupus-prone mice, the generation of anti-dsDNA and antichromatin autoantibodies is specifically inhibited. Other autoantibodies, such as anti-Sm, are maintained and even increased in TLR9-deficient mice. In contrast, ablation of TLR3, a receptor for dsRNA, did not inhibit the formation of autoantibodies to either RNA- or DNA-containing antigens. Surprisingly, we found that despite the lack of anti-dsDNA autoantibodies in TLR9-deficient mice, there was no effect on the development of clinical autoimmune disease or nephritis. These results demonstrate a specific requirement for TLR9 in autoantibody formation in vivo and indicate a critical role for innate immune activation in autoimmunity. |
