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Monocytes from Irf5−/− Mice Have an Intrinsic Defect in Their Response to Pristane-Induced Lupus
- Source :
- The Journal of Immunology. 189:3741-3750
- Publication Year :
- 2012
- Publisher :
- The American Association of Immunologists, 2012.
-
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.
- Subjects :
- CCR2
Immunology
Inflammation
Biology
CCL2
Article
Monocytes
Mice
Peritoneal cavity
Chemokine receptor
Cell Movement
medicine
Animals
Antigens, Ly
Humans
Lupus Erythematosus, Systemic
Immunology and Allergy
skin and connective tissue diseases
Peritoneal Cavity
Mice, Knockout
Systemic lupus erythematosus
Terpenes
Monocyte
medicine.disease
Mice, Inbred C57BL
HEK293 Cells
medicine.anatomical_structure
Interferon Regulatory Factors
medicine.symptom
IRF5
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 189
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....4fdd90c1acf7dda115ec94ce93f4473b