Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells

Yi Ting Koh, John C. Scatizzi, Jennifer D. Gahan, Brian R. Lawson, Roberto Baccala, K. Michael Pollard, Bruce A. Beutler, Argyrios N. Theofilopoulos, Dwight H. Kono

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Nucleic acid (NA)-sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b13d lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear autoantibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR-mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.

Original languageEnglish (US)
Pages (from-to)4982-4990
Number of pages9
JournalJournal of Immunology
Volume190
Issue number10
DOIs
StatePublished - May 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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