Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

Jixian Wang, Luokun Xie, Chenqi Yang, Changhong Ren, Kaijing Zhou, Brian Wang, Zhijun Zhang, Yongting Wang, Kunlin Jin, Guo Yuan Yang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 × 105) 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-p) 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.

Original languageEnglish
Article number361
JournalFrontiers in Cellular Neuroscience
Volume9
Issue numberSEPTEMBER
DOIs
StatePublished - 14 Sep 2015

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Neural Stem Cells
Lateral Ventricles
Regulatory T-Lymphocytes
Bromodeoxyuridine
Interleukin-10
Cell Proliferation
Neurogenesis
Brain
Stem Cells
Middle Cerebral Artery Infarction
Transforming Growth Factors
Brain Ischemia
Inbred C57BL Mouse
Heart Ventricles
Cell Movement
Ischemia
Cell Count
Stroke
In Vitro Techniques
Therapeutics

Keywords

  • Brain ischemia
  • Interleukin 10
  • Neurogenesis
  • Regulatory T cell
  • Subventricular zone

Cite this

Wang, Jixian ; Xie, Luokun ; Yang, Chenqi ; Ren, Changhong ; Zhou, Kaijing ; Wang, Brian ; Zhang, Zhijun ; Wang, Yongting ; Jin, Kunlin ; Yang, Guo Yuan. / Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10. In: Frontiers in Cellular Neuroscience. 2015 ; Vol. 9, No. SEPTEMBER.
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Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10. / Wang, Jixian; Xie, Luokun; Yang, Chenqi; Ren, Changhong; Zhou, Kaijing; Wang, Brian; Zhang, Zhijun; Wang, Yongting; Jin, Kunlin; Yang, Guo Yuan.

In: Frontiers in Cellular Neuroscience, Vol. 9, No. SEPTEMBER, 361, 14.09.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

AU - Wang, Jixian

AU - Xie, Luokun

AU - Yang, Chenqi

AU - Ren, Changhong

AU - Zhou, Kaijing

AU - Wang, Brian

AU - Zhang, Zhijun

AU - Wang, Yongting

AU - Jin, Kunlin

AU - Yang, Guo Yuan

PY - 2015/9/14

Y1 - 2015/9/14

N2 - 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 × 105) 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-p) 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.

AB - 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 × 105) 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-p) 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.

KW - Brain ischemia

KW - Interleukin 10

KW - Neurogenesis

KW - Regulatory T cell

KW - Subventricular zone

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