Regulation of Central Nervous System Myeloid-Derived Suppressor Cells in the Crucial Role of Granulocytic

There is a need in autoimmune diseases to uncover the mechanisms involved in the natural resolution of inflammation. In this article, we demonstrate that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. In vivo transfer of G-MDSCs ameliorated experimental autoimmune encephalomyelitis, significantly decreased demyelination, and delayed disease onset through inhibition of encephalitogenic Th1 and Th17 immune responses. Exposure of G-MDSCs to the autoimmune milieu led to up-regulation of the programmed death 1 ligand that was required for the G-MDSC– mediated suppressive function both in vitro and in vivo. Importantly, myeloid-derived suppressor cells were enriched in the periphery of subjects with active multiple sclerosis and suppressed the activation and proliferation of autologous CD4 + T cells ex vivo. Collectively, this study revealed a pivotal role for myeloid-derived suppressor cells in the regulation of multiple sclerosis, which could be exploited for therapeutic purposes. The Journal of Immunology , 2012, 188: 1136–1146. e-establishment of immune homeostasis and self-tol-erance remain unresolved issues in autoimmune inflammatory diseases. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS of unknown eti-ology (1). Experimental autoimmune encephalomyelitis CD4 + CD25 2 autologous T cells. These results demonstrated that PD-L1 expression by human CD33 + CD15 + MDSCs might be involved in MDSC-mediated suppression and indicated that other mediators have to participate, because blocking of PD-L1 does not fully restore human T cell proliferation. Overall, our results demonstrated a significant enrichment of G-MDSCs in active MS patients with a potent ability to suppress the activation and expansion of autologous T cells.