Background/Purpose Although myeloid-derived suppressor cells (MDSCs) have been linked to T-cell tolerance, their role in rheumatoid arthritis (RA) remains exclusive. Here, we investigated the potential association of MDSCs with the disease pathogenesis using specimen collected from RA patients and the experimental model of collagen-induced arthritis (CIA).

Methods The frequency of MDSCs in the peripheral blood and the synovial fluids of RA patients (n = 59), osteoarthritis patients (OA, n = 15), and healthy individuals (n = 20) was detected by flow cytometry. And their association with the disease severity and the levels of IL-17A was analyzed. Similarly, MDSCs in the peripheral blood, lymphoid tissues, inflamed paws, or synovial fluid and their association with disease severity, tissue inflammation, and the levels of pathogenic T-helper (Th) 17 cells was examined in CIA mice. The MDSCs in arthritic mice were also characterized for their phenotype, inflammation status, T-cell suppressive activity, and their capacity of pro-Th17 cell differentiation. The contribution of MDSCs to Th17 response was examined by co-culturing MDSCs with naïve CD4⁺ T cells under Th17-polarizing conditions both in RA patients and mice. Moreover, their pathogenic role in RA was further revealed by antibody depletion of MDSCs in CIA mice. 

Results MDSCs expanded significantly in RA patients and in CIA mice, which were correlated positively with disease severity and an inflammatory Th17 response. While displaying T-cell suppressive activity, MDSCs from arthritic mice produced high levels of inflammatory cytokines (e.g., IL-1β, and TNF-a). Both human MDSCs (CD11b⁺CD33⁺) and mouse MDSCs (CD11b⁺Gr-1⁺) efficiently promoted Th17 cell polarization ex vivo. Elimination of MDSCs in CIA mice markedly ameliorated disease symptoms concomitant with reduced levels of Th17 cells.

Conclusion Our studies revealed the unrecognized pathogenic role of MDSCs in RA with the capacity of driving Th17 cell differentiation. This cell population might be served as novel therapeutic target for RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/myeloid-derived-suppressor-cells-in-rheumatoid-arthritis-friend-or-foe/