Myeloid-Derived Suppressor Cells in Inflammatory Arthritis

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cell populations with potent immunosuppressive activity. MDSCs accumulate during states of chronic inflammation in response to inflammatory cytokine signaling that triggers emergency myelopoiesis in the bone marrow. In rheumatoid arthritis and experimental models of inflammatory arthritis, MDSCs were initially thought to serve as a regulatory checkpoint that limits excessive inflammation. However, subsequent studies have shown that these cells can either alleviate or worsen arthritis depending on immunophenotype, disease timing, microenvironment, cytokines/chemokines, and transcriptional states. Taken together, the seemingly paradoxical roles of MDSCs in inflammatory arthritis likely reflect a highly plastic and context-dependent myeloid continuum. This review examines current knowledge of MDSCs in inflammatory arthritis, highlighting the conditions that direct their functional diversity and the factors that determine whether they alleviate or exacerbate disease. We also discuss emerging therapeutic strategies and emerging concepts to better understand these immune cell populations in the context of inflammatory arthritis.