Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus.
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ABSTRACT:
SUBMITTER: Kono DH
PROVIDER: S-EPMC2715524 | biostudies-literature | 2009 Jul
REPOSITORIES: biostudies-literature
Publications
Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus.
Kono Dwight H DH Haraldsson M Katarina MK Lawson Brian R BR Pollard K Michael KM Koh Yi Ting YT Du Xin X Arnold Carrie N CN Baccala Roberto R Silverman Gregg J GJ Beutler Bruce A BA Theofilopoulos Argyrios N AN
Proceedings of the National Academy of Sciences of the United States of America 20090702 29
Using the Unc93b1 3d mutation that selectively abolishes nucleic acid-binding Toll-like receptor (TLR) (TLR3, -7, -9) signaling, we show these endosomal TLRs are required for optimal production of IgG autoAbs, IgM rheumatoid factor, and other clinical parameters of disease in 2 lupus strains, B6-Fas(lpr) and BXSB. Strikingly, treatment with lipid A, an autoAb-inducing TLR4 agonist, could not overcome this requirement. The 3d mutation slightly reduced complete Freund's adjuvant (CFA)-mediated ant ...[more]
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