摘要
Astrocytes are believed to bridge interactions between infiltrating lymphocytes and neurons during brain ischemia, but the mechanisms for this action are poorly understood. Here we found that interleukin-15 (IL-15) is dramatically up-regulated in astrocytes of postmortem brain tissues from patients with ischemic stroke and in a mouse model of transient focal brain ischemia. We generated a glial fibrillary acidic protein (GFAP) promoter-controlled IL-15-expressing transgenic mouse (GFAP-IL-15(tg)) line and found enlarged brain infarcts, exacerbated neurodeficits after the induction of brain ischemia. In addition, knockdown of IL-15 in astrocytes attenuated ischemic brain injury. Interestingly, the accumulation of CD8(+) T and natural killer (NK) cells was augmented in these GFAP-IL-15(tg) mice after brain ischemia. Of note, depletion of CD8(+) T or NK cells attenuated ischemic brain injury in GFAP-IL-15(tg) mice. Furthermore, knockdown of the IL-15 receptor a or blockade of cell-to-cell contact diminished the activation and effector function of CD8(+) T and NK cells in GFAP-IL-15(tg) mice, suggesting that astrocytic IL-15 is delivered in trans to target cells. Collectively, these findings indicate that astrocytic IL-15 could aggravate postischemic brain damage via propagation of CD8(+) T and NK cell-mediated immunity.
- 出版日期2017-1-17
- 单位天津市环湖医院; 天津医科大学