DOI: 10.1084/jem.20050338. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus

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

10.1084/jem.20050338

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

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.

Bibliography

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. The Journal of Experimental Medicine, 202(2), 321â331.

Authors 6

Sean R. Christensen (first)
Michael Kashgarian (additional)
Lena Alexopoulou (additional)
Richard A. Flavell (additional)
Shizuo Akira (additional)
Mark J. Shlomchik (additional)

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Dates

Type	When
Created	20 years, 1 month ago (July 18, 2005, 3:03 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 9:21 a.m.)
Indexed	3 days, 1 hour ago (Sept. 3, 2025, 6:15 a.m.)
Issued	20 years, 1 month ago (July 18, 2005)
Published	20 years, 1 month ago (July 18, 2005)
Published Online	20 years, 1 month ago (July 18, 2005)
Published Print	20 years, 1 month ago (July 18, 2005)

Funders 0

None

BibTeX

@article{Christensen_2005, title={Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus}, volume={202}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20050338}, DOI={10.1084/jem.20050338}, number={2}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Christensen, Sean R. and Kashgarian, Michael and Alexopoulou, Lena and Flavell, Richard A. and Akira, Shizuo and Shlomchik, Mark J.}, year={2005}, month=jul, pages={321–331} }

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