Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

Multiple sclerosis ( MS ) is a chronic autoimmune disease of the central nervous system involving dysregulated encephalitogenic T cells. Myeloid‐derived suppressor cells ( MDSC s) have been recognized for their important function in regulating T‐cell responses. Recent studies have indicated a role for MDSC s in autoimmune diseases, but their significance in MS is not clear. Here, we assessed the frequencies of CD 14 + HLA ‐ DR low monocytic MDSC s (Mo‐ MDSC s) and CD 33 + CD 15 + CD 11b + HLA ‐ DR low granulocytic MDSC s (Gr‐ MDSC s) and investigated phenotypic and functional differences of Mo‐ MDSC s at different clinical stages of MS and in healthy subjects ( HC ). Increased frequencies of Mo‐ MDSC s ( P  <   0.05) and Gr‐ MDSC s ( P  <   0.05) were observed in relapsing‐remitting MS patients during relapse ( RRMS ‐relapse) compared to stable RRMS ( RRMS ‐rem). Secondary progressive MS ( SPMS ) patients displayed a decreased frequency of Mo‐ MDSC s and Gr‐ MDSC s compared to HC ( P  <   0.05). Mo‐ MDSC s within RRMS patients expressed significantly higher cell surface protein levels of CD 86 and CD 163 compared to SPMS patients. Mo‐ MDSC s within SPMS exhibited decreased mRNA expression of interleukin‐10 and heme oxygenase 1 compared to RRMS and HC . Analysis of T‐cell regulatory function of Mo‐ MDSC s demonstrated T‐cell suppressive capacity in RRMS and HC s, while Mo‐ MDSC s of SPMS promoted autologous T‐cell proliferation, which aligned with a differential cytokine profile compared to RRMS and HC s. This study is the first to show phenotypic and functional shifts of MDSC s between clinical stages of MS , suggesting a role for MDSC s as a therapeutic target to prevent MS disease progression.