RESUMEN
Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4(+)T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4(+)T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4(+)T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4(+)GITR(+)T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR-GITR ligand (GITRL) interaction by GITR-Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4(+)T cells, GITR(+)CD4(+)T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR-GITRL interaction may be a novel immune-based therapy in stroke.
Asunto(s)
Isquemia Encefálica/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Células-Madre Neurales/citología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/metabolismo , Animales , Isquemia Encefálica/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Citometría de Flujo , Inmunohistoquímica , Masculino , Ratones , Reacción en Cadena de la Polimerasa , Accidente Cerebrovascular/patologíaRESUMEN
The results of application of hitamine, enterosorbent of marine origin, by the patients with chronic noncalculous cholecystitis in the remission phase are cited. It has been established that dietotheraphy in complex with hitamine renders the antiinflammatory and lipidcorrected action, favours the increase of remission terms.