論文 - 詳細
| RRC ID | 12685 |
|---|---|
| 著者 | Takata M, Nakagomi T, Kashiwamura S, Nakano-Doi A, Saino O, Nakagomi N, Okamura H, Mimura O, Taguchi A, Matsuyama T. |
| タイトル | Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke. |
| ジャーナル | Cell Death Differ |
| Abstract |
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. |
| 巻・号 | 19(5) |
| ページ | 756-67 |
| 公開日 | 2012-5-1 |
| DOI | 10.1038/cdd.2011.145 |
| PII | cdd2011145 |
| PMID | 22052192 |
| PMC | PMC3321616 |
| MeSH | Animals Brain Ischemia / metabolism* Brain Ischemia / pathology CD4-Positive T-Lymphocytes / metabolism* Cerebral Cortex / metabolism Cerebral Cortex / pathology Flow Cytometry Glucocorticoid-Induced TNFR-Related Protein / metabolism* Immunohistochemistry Male Mice Neural Stem Cells / cytology* Polymerase Chain Reaction Stroke / immunology* Stroke / metabolism* Stroke / pathology |
| IF | 10.717 |
| 引用数 | 30 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC00267 |