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 journalArticle

28 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

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Koh, Y. T., Scatizzi, J. C., Gahan, J. D., Lawson, B. R., Baccala, R., Pollard, K. M., Beutler, B. A., Theofilopoulos, A. N., & Kono, D. H. (2013). Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells. Journal of Immunology, 190(10), 4982-4990. https://doi.org/10.4049/jimmunol.1202986