title: Novel feedback loop between M2 macrophages/microglia and regulatory B cells in estrogen-protected EAE mice.
abstract: Immunoregulatory sex hormones, including estrogen and estriol, may prevent relapses in multiple sclerosis during pregnancy. Our previous studies have demonstrated that regulatory B cells are crucial for estrogen-mediated protection against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of alternatively activated (M2) macrophages/microglia that results in an increased frequency of regulatory B cells in the spinal cord of estrogen treated mice with EAE. We further demonstrate that cultured M2-polarized microglia promote the induction of regulatory B cells. Our study suggests that estrogen neuroprotection induces a regulatory feedback loop between M2 macrophages/microglia and regulatory B cells.
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Benedek
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Ha
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Kent
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Seifert
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA; Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address: offnerva@ohsu.edu.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D013116:Spinal Cord / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D004967:Estrogens; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: EAE; Estrogen; IL-10; M1/2 microglia; Regulatory B cells