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) |
|---|---|
| Pages (from-to) | 324-330 |
| Number of pages | 7 |
| Journal | Translational Stroke Research |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2012 |
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Keywords
- Bregs
- Experimental stroke
- IL-10
- Immunotherapy
- PD-1
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Cardiology and Cardiovascular Medicine
Cite this
A Novel Hypothesis : Regulatory B Lymphocytes Shape Outcome from Experimental Stroke. / Offner, Halina; Hurn, Patricia D.
In: Translational Stroke Research, Vol. 3, No. 3, 09.2012, p. 324-330.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Novel Hypothesis
T2 - Regulatory B Lymphocytes Shape Outcome from Experimental Stroke
AU - Offner, Halina
AU - Hurn, Patricia D.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Bregs
KW - Experimental stroke
KW - IL-10
KW - Immunotherapy
KW - PD-1
UR - http://www.scopus.com/inward/record.url?scp=84865707531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865707531&partnerID=8YFLogxK
U2 - 10.1007/s12975-012-0187-4
DO - 10.1007/s12975-012-0187-4
M3 - Article
C2 - 23175646
AN - SCOPUS:84865707531
VL - 3
SP - 324
EP - 330
JO - Translational Stroke Research
JF - Translational Stroke Research
SN - 1868-4483
IS - 3
ER -