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

Metab Brain Dis. 2013 Sep;28(3):375-86. doi: 10.1007/s11011-013-9413-3. Epub 2013 May 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / metabolism*
  • Brain Ischemia / prevention & control
  • Cerebral Infarction / metabolism*
  • Exons / genetics
  • Flow Cytometry
  • Green Fluorescent Proteins
  • Immunoglobulin mu-Chains / genetics
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammation / pathology
  • Interleukin-10 / blood*
  • Mice
  • Mice, Knockout
  • Monocytes / physiology
  • Spleen / pathology
  • Stroke / blood*

Substances

  • Immunoglobulin mu-Chains
  • Interleukin-10
  • Green Fluorescent Proteins