title: IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke.
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.
authors: Neuroimmunology Research, VA Medical Center, R&D-31, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors: Sheetal
authors: S
authors: Bodhankar
authors: Yingxin
authors: Y
authors: Chen
authors: Arthur A
authors: AA
authors: Vandenbark
authors: Stephanie J
authors: SJ
authors: Murphy
authors: Halina
authors: H
authors: Offner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000517:prevention & control; D002544:Cerebral Infarction / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology; D013154:Spleen / Q000473:pathology; D020521:Stroke / Q000097:blood*
chemical_list: D007148:Immunoglobulin mu-Chains; D016753:Interleukin-10; D049452:Green Fluorescent Proteins
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