ena-STUDY-Klinikum rechts der Isar, II. Medizinische Klinik-23-08-2018-10:38:32:095-5
Myeloid-derived suppressor cells control B cells within the central nervous system during autoimmunity
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here, we show that PMN-MDSCs have the unique capacity to restrain B cells during central nervous system (CNS) autoimmunity. Ly6G+ cells are recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interact with GM-CSF and IL-6-producing B cells, and acquire properties of PMN-MDSCs in the CNS in a STAT3-dependent manner. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 results in selective expansion of GM-CSF producing B cells in the CNS compartment, which in turn promotes an activated microglial phenotype and failure to recover from EAE. Since in the cerebrospinal fluid of human multiple sclerosis patients, the frequency of CD138+ B cells is negatively correlated with the frequency of PMN-MDSCs, we conclude that PMN-MDSCs might selectively control activated B cells within the inflamed CNS.
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here, we show that PMN-MDSCs have the unique capacity to restrain B cells during central nervous system (CNS) autoimmunity. Ly6G+ cells are recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interact with GM-CSF and IL-6-producing B cells, and acquire properties of PMN-MDSCs in the CNS in a STAT3-dependent manner. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 results in selective expansion of GM-CSF producing B cells in the CNS compartment, which in turn promotes an activated microglial phenotype and failure to recover from EAE. Since in the cerebrospinal fluid of human multiple sclerosis patients, the frequency of CD138+ B cells is negatively correlated with the frequency of PMN-MDSCs, we conclude that PMN-MDSCs might selectively control activated B cells within the inflamed CNS.