Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus

478Citations
Citations of this article
196Readers
Mendeley users who have this article in their library.

Abstract

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. JEM © The Rockefeller University Press.

Cite

CITATION STYLE

APA

Christensen, S. R., Kashgarian, M., Alexopoulou, L., Flavell, R. A., Akira, S., & Shlomchik, M. J. (2005). Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. Journal of Experimental Medicine, 202(2), 321–331. https://doi.org/10.1084/jem.20050338

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free