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

• DOI: 10.1111/imcb.12042
• Publication Date: 2018-03-23T04:46:11Z
• Authors: Ellen Iacobaeus; Iyadh Douagi; Regina Jitschin; Maritha Marcusson...; Anton Törnqvist A...; Caroline Gavin; Katia Lefsihane; Lindsay C Davies; Dimitrios Mougiak...; Nadir Kadri; Katarina Le Blanc
• Keywords: Adult; Male; Multiple Sclerosis; Myeloid-Derived Suppressor Cells; Middle Aged; T-Lymphocytes, Regulatory; Immunophenotyping; 3. Good health; Immunomodulation; 03 medical and health sciences; 0302 clinical medicine; Antigens, CD; T-Lymphocyte Subsets; Disease Progression; Cytokines; Humans; Female; Immunotherapy; Cells, Cultured; Cell Proliferation

AbstractMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system involving dysregulated encephalitogenic T cells. Myeloid‐derived suppressor cells (MDSCs) have been recognized for their important function in regulating T‐cell responses. Recent studies have indicated a role for MDSCs in autoimmune diseases, but their significance in MS is not clear. Here, we assessed the frequencies of CD14+HLA‐DRlow monocytic MDSCs (Mo‐MDSCs) and CD33+CD15+CD11b+HLA‐DRlow granulocytic MDSCs (Gr‐MDSCs) and investigated phenotypic and functional differences of Mo‐MDSCs at different clinical stages of MS and in healthy subjects (HC). Increased frequencies of Mo‐MDSCs (P < 0.05) and Gr‐MDSCs (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‐MDSCs and Gr‐MDSCs compared to HC (P < 0.05). Mo‐MDSCs within RRMS patients expressed significantly higher cell surface protein levels of CD86 and CD163 compared to SPMS patients. Mo‐MDSCs 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‐MDSCs demonstrated T‐cell suppressive capacity in RRMS and HCs, while Mo‐MDSCs of SPMS promoted autologous T‐cell proliferation, which aligned with a differential cytokine profile compared to RRMS and HCs. This study is the first to show phenotypic and functional shifts of MDSCs between clinical stages of MS, suggesting a role for MDSCs as a therapeutic target to prevent MS disease progression.