title: Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10.
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 × 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-β) 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.
authors.affiliation: Department of Neurology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China ; Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai, China ; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Jixian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Luokun
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Chenqi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Changhong
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Kaijing
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Wang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center Fort Worth, TX, USA.
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Neurology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China ; Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
keywords: brain ischemia; interleukin 10; neurogenesis; regulatory T cell; subventricular zone