title: Estrogen induces multiple regulatory B cell subtypes and promotes M2 microglia and neuroprotection during experimental autoimmune encephalomyelitis.
abstract: Sex hormones promote immunoregulatory effects on multiple sclerosis. The current study evaluated estrogen effects on regulatory B cells and resident CNS microglia during experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of multiple regulatory B cell markers indicative of IL-10 dependent as well as IFN-γ dependent pathways. Moreover, although estrogen pretreatment of EAE mice inhibited the infiltration of pro-inflammatory cells into the CNS, it enhanced the frequency of regulatory B cells and M2 microglia. Our study suggests that estrogen has a broad effect on the development of regulatory B cells during EAE, which in turn could promote neuroprotection.
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: Sheetal
authors.initials: S
authors.lastname: Bodhankar
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: Kelley
authors.initials: K
authors.lastname: Jordan
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: Dustin
authors.initials: D
authors.lastname: Manning
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; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D004958:Estradiol / Q000627:therapeutic use*; D005620:Freund's Adjuvant / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D037342:Pertussis Toxin / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013154:Spleen / Q000166:cytology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55); D004958:Estradiol; D005620:Freund's Adjuvant; D037342:Pertussis Toxin
keywords: EAE; Estrogen; IFN-γ; IL-10; Microglia; Regulatory B cell