Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse

Abstract

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. 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. CD11b(+) GR-1(low) cells had a suppressive effect on CD4(+) T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b(+) GR-1(low) cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b(+) GR-1(low) cells increased in the presence of monocyte chemoattractant protein-1/CCL2. We assessed the involvement of CD11b(+) GR-1(low) 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.