title: Treatment of experimental stroke with IL-10-producing B-cells reduces infarct size and peripheral and CNS inflammation in wild-type B-cell-sufficient mice.
abstract: Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. 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 CNS damage after middle cerebral artery occlusion (MCAO) that could be prevented by transfer of IL-10(+) B-cells. The purpose of this study was to determine if the beneficial immunoregulatory effects on MCAO of the IL-10(+) B-cell subpopulation also extends to B-cell-sufficient mice that would better represent stroke subjects. CNS inflammation and infarct volumes were evaluated in male C57BL/6J (WT) mice that received either RPMI or IL-10(+) B-cells and underwent 60 min of middle cerebral artery occlusion (MCAO) followed by 96 h of reperfusion. Transfer of IL-10(+) B-cells markedly reduced infarct volume in WT recipient mice when given 24 h prior to or 4 h after MCAO. B-cell protected (24 h pre-MCAO) mice had increased regulatory subpopulations in the periphery, reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres of the IL-10(+) B-cell-treated group. Moreover, transfer of IL-10(+) B-cells 24 h before MCAO led to a significant preservation of regulatory immune subsets in the IL-10(+) B-cell protected group presumably indicating their role in immunomodulatory mechanisms, post-stroke. Our studies are the first to demonstrate a major immunoregulatory role for IL-10(+) regulatory B-cells in preventing and treating MCAO in WT mice and also implicating their potential role in attenuating complications due to post-stroke immunosuppression.
authors.affiliation: Neuroimmunology Research, VA Medical Center, Portland, OR, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bodhankar
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Chen
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Murphy
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D001921:Brain / Q000276:immunology / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D017930:Genes, Reporter; D007121:Immunocompetence; D018189:Immunomagnetic Separation; D056747:Immunomodulation; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy*; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D018941:Antigens, CD19; C556062:IL10 protein, mouse; D016753:Interleukin-10