调节性B细胞
TLR9型
过继性细胞移植
脾脏
T细胞
细胞生物学
白细胞介素10
医学
生物
实验性自身免疫性脑脊髓炎
免疫学
化学
炎症
细胞因子
免疫系统
基因表达
DNA甲基化
基因
生物化学
作者
Jinsheng Hong,Jie Fang,Ruilong Lan,Qi Tan,Yeping Tian,Mei Zhang,Paul Okunieff,Lurong Zhang,Jianhua Lin,Deping Han
标识
DOI:10.1016/j.molimm.2017.01.011
摘要
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%–3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5 Gy or 10 Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9−/− mice. TLR9 agonist ODN1826 stimulation in vitro for 5 h induced more B10 cells to express cytoplasmic IL-10 in sub-TBI WT mice than in TLR9−/− mice. Prolonged ODN1826 stimulation (48 h) induced additional spleen CD19hiCD5+CD1dhi B cells to express IL-10. TLR9-dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub-TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub-TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub-TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.
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