Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 202, Issue 9, Pages 1171-1177Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20050630
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI36529, P01 AI036529] Funding Source: Medline
- NIAMS NIH HHS [P01 AR050256, AR35230, AR050256, R01 AR035230] Funding Source: Medline
Ask authors/readers for more resources
Previous studies (Leadbetter, E. A., I. R. Rifkin, A. H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416: 603 - 607; Viglianti, G. A., C. M. Lau, T. M. Hanley, B. A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19: 837 - 847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-alpha, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available