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Nat Immunol. 2018 Dec;19(12):1341-1351. doi: 10.1038/s41590-018-0237-5. Epub 2018 Oct 29.

Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity.

Author information

1
Department of Experimental Neuroimmunology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
2
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
3
Institute of Molecular Oncology and Functional Genomics, TranslaTUM Cancer Center, Technical University of Munich, Munich, Germany.
4
Department of Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
5
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University Munich, Munich, Germany.
6
Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany.
7
Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
8
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
9
Department of Pathology and Immunology, Division of Clinical Pathology, University of Geneva, Geneva, Switzerland.
10
Department of Experimental Neuroimmunology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. thomas.korn@tum.de.
11
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. thomas.korn@tum.de.
12
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. thomas.korn@tum.de.

Abstract

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS.

PMID:
30374128
PMCID:
PMC6241855
DOI:
10.1038/s41590-018-0237-5
[Indexed for MEDLINE]
Free PMC Article

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