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

26 Citations (Scopus)

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

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Antibody-Producing Cells
Autoantibodies
Nucleic Acids
Anti-Idiotypic Antibodies
B-Lymphocytes
Systemic Lupus Erythematosus
Autoimmune Diseases
Rheumatoid Factor
Autoimmunity

ASJC Scopus subject areas

  • Immunology

Cite this

Koh, Y. T., Scatizzi, J. C., Gahan, J. D., Lawson, B. R., Baccala, R., Pollard, K. M., ... 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

Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells. / Koh, Yi Ting; Scatizzi, John C.; Gahan, Jennifer D.; Lawson, Brian R.; Baccala, Roberto; Pollard, K. Michael; Beutler, Bruce A.; Theofilopoulos, Argyrios N.; Kono, Dwight H.

In: Journal of Immunology, Vol. 190, No. 10, 15.05.2013, p. 4982-4990.

Research output: Contribution to journalArticle

Koh, YT, Scatizzi, JC, Gahan, JD, Lawson, BR, Baccala, R, Pollard, KM, Beutler, BA, Theofilopoulos, AN & Kono, DH 2013, 'Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells', Journal of Immunology, vol. 190, no. 10, pp. 4982-4990. https://doi.org/10.4049/jimmunol.1202986
Koh, Yi Ting ; Scatizzi, John C. ; Gahan, Jennifer D. ; Lawson, Brian R. ; Baccala, Roberto ; Pollard, K. Michael ; Beutler, Bruce A. ; Theofilopoulos, Argyrios N. ; Kono, Dwight H. / Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells. In: Journal of Immunology. 2013 ; Vol. 190, No. 10. pp. 4982-4990.
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