Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2015.00361
Keywords
brain ischemia; interleukin 10; neurogenesis; regulatory T cell; subventricular zone
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Funding
- US Public Health Service [NS57186, AG21980]
- National Natural Science Foundation of China [U1232205, 81371305]
- Science and Technology Commission of Shanghai Municipality [13ZR1422600]
- KC Wong Foundation
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Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs (1 x 10(5)) were injected into the left lateral ventricle (LV) of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-beta) signaling. We found that the number of BrdU(+) cells in the SVZ was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU(+) cells expressed Mash1. Blocking IL-10 reduced the number of Mash1(+)/BrdU(+) cells, but increased the amount of GFAP(+)/BrdU(+) cells. Here, we conclude that activated Tregs enhanced neural stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted NSC proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke.
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