Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus

David A. Savitsky, Hideyuki Yanai, Tomohiko Tamura, Tadatsugu Taniguchi, Kenya Honda

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Interferon regulatory factor (IRF) 5 is a key transcription factor for the activation of innate immune responses downstream of Toll-like receptor signaling. Based on recent genetic analyses, IRF5 is a focus for its potential involvement in systemic lupus erythematosus (SLE), although how IRF5 contributes to SLE is uncertain. In this study, we demonstrate a requirement for IRF5 in the development of murine SLE via its role in B lymphocytes. We show that antinuclear autoantibodies and Ig glomerular deposits, hallmarks of SLE, are absent in Irf5-/- mice challenged to develop SLE by pristane injection. In particular, production of autoantibodies of the IgG2a subtype, the most prominent isotype in inducing autoimmunity, requires IRF5. Finally, we provide evidence for the critical role of this transcription factor in the secretion of pathogenic antibodies through its direct control of class switch recombination of the γ2a locus. By demonstrating a B-cell-intrinsic role, this study places IRF5 in a context that may have implications for understanding the pathogenesis of human SLE.

Original languageEnglish
Pages (from-to)10154-10159
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number22
DOIs
Publication statusPublished - 2010 Jun 1
Externally publishedYes

Fingerprint

Internal-External Control
Systemic Lupus Erythematosus
B-Lymphocytes
Autoantibodies
Transcription Factors
Interferon Regulatory Factors
Toll-Like Receptors
Autoimmunity
Innate Immunity
Transcriptional Activation
Genetic Recombination
Injections
Antibodies

Keywords

  • Autoimmunity
  • B lymphocytes
  • TLR signaling

ASJC Scopus subject areas

  • General

Cite this

Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus. / Savitsky, David A.; Yanai, Hideyuki; Tamura, Tomohiko; Taniguchi, Tadatsugu; Honda, Kenya.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 22, 01.06.2010, p. 10154-10159.

Research output: Contribution to journalArticle

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