IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke

Sheetal Bodhankar, Yingxin Chen, Arthur A. Vandenbark, Stephanie J. Murphy, Halina Offner

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Clinical stroke induces inflammatory processes leading to cerebral injury. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and increased numbers of activated T-cells, monocytes and microglial cells in the brain, thus implicating a regulatory role of B-cell subpopulations in limiting CNS damage from stroke. The aim of this study was to determine whether the IL-10-producing regulatory B-cell subset can limit CNS inflammation and reduce infarct volume following ischemic stroke in B-cell deficient (μMT-/-) mice. Five million IL-10-producing B-cells were obtained from IL-10-GFP reporter mice and transferred i.v. to μMT -/-mice. After 24 h following this transfer, recipients were subjected to 60 min of middle cerebral artery occlusion (MCAO) followed by 48 h of reperfusion. Compared to vehicle-treated controls, the IL-10+ B-cell-replenished μMT-/-mice had reduced infarct volume and fewer infiltrating activated T-cells and monocytes in the affected brain hemisphere. These effects in CNS were accompanied by significant increases in regulatory T-cells and expression of the co-inhibitory receptor, PD-1, with a significant reduction in the proinflammatory milieu in the periphery. These novel observations provide the first proof of both immunoregulatory and protective functions of IL-10-secreting B-cells in MCAO that potentially could impart significant benefit for stroke patients in the clinic.

Original languageEnglish (US)
Pages (from-to)375-386
Number of pages12
JournalMetabolic brain disease
Volume28
Issue number3
DOIs
StatePublished - Sep 1 2013

Keywords

  • IL-10
  • Inflammatory cells
  • MCAO
  • Regulatory B-cells

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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