TY - JOUR
T1 - Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke
AU - Ren, Xuefang
AU - Akiyoshi, Kozaburo
AU - Dziennis, Suzan
AU - Vandenbark, Arthur A.
AU - Herson, Paco S.
AU - Hurn, Patricia D.
AU - Offner, Halina
PY - 2011/6/8
Y1 - 2011/6/8
N2 - Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient /xMT mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated /xMT versus WT mice. These MCAO-induced changes were completely prevented in B-cell-restored /xMT mice after transfer of highly purified WT GFP + B cells that were detected in the periphery, but not the CNS. In contrast, transfer of B cells from IL-10 mice had no effect on infarct volume when transferred into /xMT mice. These findings strongly support a previously unrecognized activity of IL-10-secreting WT B cells to limit infarct volume, mortality rate, recruitment of inflammatory cells, and functional neurological deficits 48 h after MCAO. Our novel observations are the first to implicate IL-10-secreting B cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B cells might have application as a novel therapy for this devastating neurologic condition.
AB - Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient /xMT mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated /xMT versus WT mice. These MCAO-induced changes were completely prevented in B-cell-restored /xMT mice after transfer of highly purified WT GFP + B cells that were detected in the periphery, but not the CNS. In contrast, transfer of B cells from IL-10 mice had no effect on infarct volume when transferred into /xMT mice. These findings strongly support a previously unrecognized activity of IL-10-secreting WT B cells to limit infarct volume, mortality rate, recruitment of inflammatory cells, and functional neurological deficits 48 h after MCAO. Our novel observations are the first to implicate IL-10-secreting B cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B cells might have application as a novel therapy for this devastating neurologic condition.
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U2 - 10.1523/JNEUROSCI.1623-11.2011
DO - 10.1523/JNEUROSCI.1623-11.2011
M3 - Article
C2 - 21653859
AN - SCOPUS:79958265647
SN - 0270-6474
VL - 31
SP - 8556
EP - 8563
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 23
ER -