Published in:
01-10-2010 | Original Article
Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse
Published in: Clinical and Experimental Nephrology | Issue 5/2010
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Objective
Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice.
Methods
MDSCs were analyzed by flow cytometric staining of CD11b+ GR-1+ in MRL-Fas
lpr
mice. CD4+ T-cell proliferation assay was performed by coculture with CD11b+ GR-1+ splenocytes. The percentage of immunosuppressive cells was examined during disease progression. Expression of chemokine receptor on immunosuppressive cells was analyzed, and chemotaxis assay was performed.
Results
CD11b+ GR-1low cells had a suppressive effect on CD4+ T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b+ GR-1low cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b+ GR-1low cells increased in the presence of monocyte chemoattractant protein-1/CCL2.
Conclusion
We assessed the involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas
lpr
mice. These cells regulate immunological responses via CCL2/CCR2 signaling. The regulation of immunosuppressive monocytes may provide novel therapeutic strategy for organ damage in autoimmune diseases.