Abstract
Although inflammatory immune cells clearly contribute to the development of middle cerebral artery occlusion (MCAO) in mice, the failure to block neutrophil-associated injury in clinical stroke trials has discouraged further development of immunotherapeutic approaches. However, there is renewed interest in a possible protective role for regulatory T and B cells that can suppress inflammation and limit central nervous system damage induced by infiltrating pro-inflammatory cells. Our failure to implicate CD4+FoxP3+ T cells in limiting brain lesion volume after MCAO turned our focus towards regulatory B cells known to mediate protection against other inflammatory CNS conditions. Our results clearly demonstrated that B cell-deficient mice developed larger infarct volumes, higher mortality, and more severe functional deficits compared to wild-type mice and had increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere. These MCAO-induced changes were completely prevented in B cell-restored mice after transfer of highly purified WT B cells but not IL-10-deficient B cells. 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.
Original language | English (US) |
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Pages (from-to) | 324-330 |
Number of pages | 7 |
Journal | Translational Stroke Research |
Volume | 3 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2012 |
Keywords
- Bregs
- Experimental stroke
- IL-10
- Immunotherapy
- PD-1
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Cardiology and Cardiovascular Medicine