Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

Jun Zhang, Andrew Lapato, Sheetal Bodhankar, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1117-1127
Number of pages11
JournalMetabolic Brain Disease
Volume30
Issue number5
DOIs
StatePublished - Oct 10 2015

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Regulatory B-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Interleukin-10
B-Lymphocytes
Cells
Inflammation
Death Domain Receptors
T-cells
Macrophages
Multiple Sclerosis
Gonadal Steroid Hormones
Hinges
Estradiol
Estrogens
Animals
Therapeutics
Ligands
Microglia
Demyelinating Diseases
Regulatory T-Lymphocytes

Keywords

  • B cell deficiency
  • EAE
  • Estrogen
  • IL-10
  • Regulatory B cell
  • Regulatory T cell

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice. / Zhang, Jun; Lapato, Andrew; Bodhankar, Sheetal; Vandenbark, Arthur; Offner, Halina.

In: Metabolic Brain Disease, Vol. 30, No. 5, 10.10.2015, p. 1117-1127.

Research output: Contribution to journalArticle

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