Foxp3+调节性T细胞在电针改善脓毒症后期免疫抑制中的作用研究
批准号:
81471560
项目类别:
面上项目
资助金额:
70.0 万元
负责人:
宋建钢
依托单位:
学科分类:
H1104.炎症、感染与免疫
结题年份:
2018
批准年份:
2014
项目状态:
已结题
项目参与者:
陈雪梅、许今、郑蓓洁、陈灵科、朱辉、刘晓华
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中文摘要
近期研究表明,脓毒症死亡的主因是后期免疫抑制引起的继发感染。Foxp3+调节性T细胞(Treg)的异常增多是导致免疫抑制的关键原因。我们前期研究显示,电针可激活交感和迷走神经,在二者协同作用下,调节固有免疫对内毒素的应答。鉴于Foxp3+ Treg表达胆碱能和肾上腺素能受体,且自主神经功能下降时,Foxp3+Treg数目增多,我们推测:脓毒症后期实施电针,可激活交感和(或)迷走神经,减少Foxp3+ Treg,增强对继发感染的抵抗力。本项目拟采用脓毒症后期继发感染军团菌的大鼠模型,观察电针对Foxp3+ Treg、CD4+ T细胞和继发感染的影响,通过Foxp3+ Treg过继转移、膈下迷走神经切断、化学交感阻断等方法,明确Foxp3+ Treg在电针改善免疫抑制中的作用及自主神经介导的调控机制。本项目从神经免疫调节角度阐释电针作用机理,为促进电针在脓毒症治疗中的临床应用提供理论依据。
英文摘要
It has been reported that the vast majority of septic patients do not die due to complications resulting from an overwhelming proinflammatory immune response but due to secondary/opportunistic infections resulting from a severely suppressed immune response in the later phase of sepsis. Recently, accumulating evidence have demonstrated that a significant increase in Foxp3+ Regulatory T cells (Tregs) number and suppressive function makes them an important participant in the sepsis-induced immunosuppression. Our previous study indicated that Electroacupuncture can modulate the response of the innate immune system to endotoxin via activation of both periphery sympathetic and parasympathetic systems. As Foxp3+ Treg cells express adrenergic and acetylcholine receptors, and chemical sympathectomy or vagotomy induces an increase in the number of peripheral Tregs, we hypothesized that in the later phase of sepsis application of Electroacupuncture could decrease the number and function of Foxp3+ Treg cells via activation of sympathetic and/or parasympathetic systems, which may result in enhancing CD4+ T cells proliferation, reducing the levels of bacteria in spleen, and markedly improving survival of L. pneumophila infection. Based on a sepsis surviving rat model which was challenged with secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella, we observed the effects of Electroacupuncture on the number and function of Foxp3+ Treg and CD4+ T cells, and susceptibility to L. pneumophila. Also, the key role of Foxp3+ Treg cells modulation mediated by autonomic nervous system in the immune-enhancing effects of Electroacupuncture was determined by Foxp3+ Treg cells adoptive Transfer, chemical sympathectomy, vagotomy, and so on. In this study, we attempted to clarify underlying mechanisms of Electroacupuncture-induced immunostimulation from a neuroimmune perspective, which may provide rationale for the development of Electroacupuncture as a treatment for the sepsis-induced immunosuppression.
近期研究表明,脓毒症死亡的主因是后期免疫抑制引起的继发感染。Foxp3+调节性 T细胞(Treg)的异常增多是导致免疫抑制的关键原因。我们前期研究显示,电针可激活交感和迷走神经,在二者协同作用下,调节固有免疫对内毒素的应答。鉴于 Foxp3+ Treg表达胆碱能和肾上腺素能受体,且自主神经功能下降时,Foxp3+Treg数目增多,我们推测:脓毒症后期实施电针,可激活交感和(或)迷走神经,减少Foxp3+ Treg,增强对继发感染的抵抗力。本项目采用了脓毒症后期继发腹腔感染的小鼠鼠模型,观察电针对 Foxp3+ Treg、CD4+ T细胞和继发感染清除及死亡率的影响,通过 Foxp3+ Treg过继转移或者抗体拮抗法,明确 Foxp3+ Treg在电针改善免疫抑制中的作用。结果显示脓毒症后期小鼠处于免疫抑制状态,CLP腹腔感染二次打击后生存率以及感染清除率皆明显下降,电针后处理可以改善小鼠脓毒症后免疫抑制,且提高CLP腹腔感染二次打击后生存率以及感染清除率,Foxp3+ Treg细胞的在其中起关键作用,Foxp3+ Treg的调节收到迷走神经及外周烟碱型乙酰胆碱受体调控,电针通过降低Foxp3+ Treg细胞的数量,改善脓毒症后免疫抑制,迷走神经及外周烟碱型乙酰胆碱受体起关键神经介导作用。本项目从神经免疫调节角度阐释电针作用机理,为促进电针在脓毒症治疗中的临床应用提供理论依据。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.
高迁移率族box-1蛋白的迷走神经调节介导电针诱导的缺血再灌注损伤中的心脏保护作用。
DOI:10.1038/srep15503
发表时间:2015-10-26
期刊:Scientific reports
影响因子:4.6
作者:Zhang J;Yong Y;Li X;Hu Y;Wang J;Wang YQ;Song W;Chen WT;Xie J;Chen XM;Lv X;Hou LL;Wang K;Zhou J;Wang XR;Song JG
通讯作者:Song JG
DOI:10.16306/j.1008-861x.2016.06.010
发表时间:2016
期刊:上海中医药大学学报
影响因子:--
作者:许明岚;解建;雍玥;宋建钢
通讯作者:宋建钢
DOI:10.16306/j.1008-861x.2017.01.017
发表时间:2017
期刊:上海中医药大学学报
影响因子:--
作者:许明岚;雍玥;解建;宋建钢
通讯作者:宋建钢
自主神经介导的血红素氧合酶-1调控在电针促进心梗后心肌组织修复中的作用研究
- 批准号:81774108
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2017
- 负责人:宋建钢
- 依托单位:
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