Myeloid-derived suppressor cells ameliorate the pathogenesis of autoimmune arthritis (P1058)

Abstract

Myeloid-derived suppressor cells (MDSCs) are subtypes of monocytes and granulocytes that suppress T cell activity in diseases like cancer and multiple sclerosis. Our previous studies suggested a subset of monocytes may act as MDSCs in autoimmune arthritis. Using the collagen-induced arthritis (CIA) model we identified an increase in the Ly6Chigh subset of monocytes in the periphery of WT mice with CIA compared to naïve mice. This subset was absent from the periphery of CCR2-deficient mice and these mice developed more severe CIA disease. Ly6Chigh monocytes isolated from immunized mice inhibited collagen-activated CD4+T cell proliferation as well as reduced the overall T cell numbers. In the presence of Ly6Chigh monocytes we observed high levels of nitric oxide in the supernatants and an increase in Annexin V positive CD4+T cells. To examine the biological role of these monocytes, we performed a cell-based treatment assay. Compared to control mice, in vivo transfer of Ly6Chigh monocytes to collagen-immunized mice resulted in delayed onset of disease, reduced joint swelling, decreased IL-6, IL-1β, and IFNγ expression in the joints and decreased IL-6 and IL-17 levels in the serum. In summary, Ly6Chigh monocytes function as MDSCs to inhibit CD4+T cell proliferation and survival. In vivo transfer of Ly6Chigh monocytes ameliorated autoimmune arthritis in the CIA model suggesting these cells could potentially be used in cell-based therapies for treatment of rheumatoid arthritis.