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 CD1dhiCD5+ 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+CD45hi 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.
Original language | English (US) |
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Pages (from-to) | 1117-1127 |
Number of pages | 11 |
Journal | Metabolic brain disease |
Volume | 30 |
Issue number | 5 |
DOIs | |
State | Published - Oct 10 2015 |
Keywords
- B cell deficiency
- EAE
- Estrogen
- IL-10
- Regulatory B cell
- Regulatory T cell
ASJC Scopus subject areas
- Biochemistry
- Clinical Neurology
- Cellular and Molecular Neuroscience