Monocytes from Irf5-/- mice have an intrinsic defect in their response to pristane-induced lupus

Lisong Yang, Di Feng, Xiaohui Bi, Rivka C. Stone, Betsy J. Barnes

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The transcription factor IFN regulatory factor (IRF)5 has been identified as a human systemic lupus erythematosus (SLE) susceptibility gene by numerous joint linkage and genome-wide association studies. Although IRF5 expression is significantly elevated in primary blood cells of SLE patients, it is not yet known how IRF5 contributes to SLE pathogenesis. Recent data from mouse models of lupus indicate a critical role for IRF5 in the production of pathogenic autoantibodies and the expression of Th2 cytokines and type I IFN. In the present study, we examined the mechanisms by which loss of Irf5 protects mice from pristane-induced lupus at early time points of disease development.We demonstrate that Irf5 is required for Ly6Chi monocyte trafficking to the peritoneal cavity, which is thought to be one of the initial key events leading to lupus pathogenesis in this model. Chemotaxis assays using peritoneal lavage from pristane-injected Irf5+/+ and Irf5-/- littermates support an intrinsic defect in Irf5-/- monocytes. We found the expression of chemokine receptors CXCR4 and CCR2 to be dysregulated on Irf5-/- monocytes and less responsive to their respective ligands, CXCL12 and CCL2. Bone marrow reconstitution experiments further supported an intrinsic defect in Irf5-/- monocytes because Irf5+/+ monocytes were preferentially recruited to the peritoneal cavity in response to pristane. Taken together, these findings demonstrate an intrinsic role for IRF5 in the response of monocytes to pristane and their recruitment to the primary site of inflammation that is thought to trigger lupus onset in this experimental model of SLE.

Original languageEnglish (US)
Pages (from-to)3741-3750
Number of pages10
JournalJournal of Immunology
Volume189
Issue number7
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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