title: Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice.
abstract: Clinical improvement during pregnancy in multiple sclerosis (MS) patients suggests that sex hormones exert potent regulatory effects on autoimmune function. Our previous studies demonstrated that estrogen- (17β-estradiol; E2) mediated protection against experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10 secreting CD1d(hi)CD5(+) B regulatory cells (Bregs) in wild type mice. Our data show that co-administration of E2 and IL-10(+) B cells ameliorates EAE disease severity and limits CNS infiltrating leukocytes in B cell deficient mice. Additionally, treatment with E2 and Bregs reduces demyelination and dramatically decreases the proportion of CD11b(+)CD45(hi) activated microglia/macrophages found in the CNS of immunized animals compared to vehicle, E2 or Breg cells alone. Furthermore, mice given E2 and Bregs exhibit increased numbers of peripheral programmed death-1 positive CD4(+)Foxp3(+) regulatory T cells (Tregs) and up-regulation of programmed death receptor-ligand-1 and CD80 expression on monocytes. Our study suggests IL-10 producing Bregs have powerful therapeutic potential as an agent against EAE when augmented with E2 treatment.
authors.affiliation: Neuroimmunology Research R&D-31, VA Portland Health Care System, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: Lapato
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bodhankar
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D016753:Interleukin-10; D004958:Estradiol