title: [Immunomodulation by inducing tolerance to E-selectin and adult neurogenesis after stroke].
abstract: Neuroblasts in the subventricular zone proliferate markedly after stroke, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, because of local inflammation. E-selectin is specifically expressed on endothelial cells, but only when the endothelium activates. Since endothelial activation occurs after stroke, E-selectin can serve as an immunologic tolerization antigen that can focus immunomodulation to regions of the vascular tree. Intranasal instillation of recombinant E-selectin will induce mucosal tolerance to that antigen with the generation of E-selectin-specific regulatory T cells (Tregs). Tregs may protect newly-generated neuroblasts from ischemic damage through 'bystander suppression' in which immunomodulatory cytokines such as TGF-β and IL-10 are released locally. In this series of experiments, we have shown that after E-selectin tolerization in permanent middle cerebral artery occlusion (pMCAO) rats Tregs transmigrate to the peri-infarct region of ischemic brain, TNF expression in the local neurovascular niche is reduced, and the survival of newly generated neuroblasts or neurons in the peri-infarct region is increased. Under these conditions, an improvement in sensorimotor function after pMCAO also occurs. E-selectin-specific Tregs can modulate the efficacy of adult neurogenesis after ischemia and promote repair after brain injury.
authors.affiliation: Department of Neurology, Tokyo Medical and Dental University Hospital, Tokyo Medical and Dental University.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019040:E-Selectin / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D055495:Neurogenesis / Q000187:drug effects / Q000276:immunology; D020521:Stroke / Q000276:immunology* / Q000503:physiopathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology
chemical_list: D019040:E-Selectin