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

• Published in: Nature immunology Vol. 19; no. 12; pp. 1341 - 1351
• Main Authors: Knier, Benjamin, Hiltensperger, Michael, Sie, Christopher, Aly, Lilian, Lepennetier, Gildas, Engleitner, Thomas, Garg, Garima, Muschaweckh, Andreas, Mitsdörffer, Meike, Koedel, Uwe, Höchst, Bastian, Knolle, Percy, Gunzer, Matthias, Hemmer, Bernhard, Rad, Roland, Merkler, Doron, Korn, Thomas
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2018; Nature Publishing Group
• Subjects: 631/250/127/1213; 631/250/2504/223/1699; 631/250/371; 631/250/38; Accumulation; Autoimmunity; B cells; Biomedical and Life Sciences; Biomedicine; Central nervous system; Cerebrospinal fluid; Cytokines; Encephalomyelitis; Experimental allergic encephalomyelitis; Gene expression; Granulocyte-macrophage colony-stimulating factor; Immunology; Infectious Diseases; Inflammation; Interleukin 6; Interleukins; Lymphocytes B; Multiple sclerosis; Nervous system; Neutrophils; Phenotypes; Stat3 protein; Suppressor cells
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-018-0237-5

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. Korn and colleagues show that PMN-MDSCs restrain B cell accumulation in the central nervous system in autoimmune inflammation.