Deletion of regulatory T cells supports the development of intestinal ischemia-reperfusion injuries.
Deletion of regulatory T cells supports the development of intestinal ischemia-reperfusion injuries.
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DOI：
10.1016/j.jss.2013.05.014
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Xuekang Yang;H. Bai;Yunchuan Wang;Jun Li;Qin Zhou;W. Cai;Juntao Han;Xiongxiang Zhu;Maolong Dong;D. Hu
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文献类型：
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作者：
Xuekang Yang;H. Bai;Yunchuan Wang;Jun Li;Qin Zhou;W. Cai;Juntao Han;Xiongxiang Zhu;Maolong Dong;D. Hu
肠缺血再灌注损伤（IRI）与外科和创伤患者的高发病率和死亡率相关。T细胞参与肠IRI的发病机制，并且T细胞耗竭已显示出抑制炎症反应并减少肠损伤。然而，T细胞促进肠道IRI的机制尚未完全清楚。调节性T细胞（Regulatory T cells，Tcells）是一种特异性T细胞亚群，可抑制免疫反应并保护组织免受损伤。我们假设，TIPs可能参与肠IRI.Materials和methodsWe受到C57/B16小鼠缺血30分钟的上级肠系膜动脉夹闭，然后再灌注。在诱导IRI之前，用抗CD 25单克隆抗体或Tcl 3过继转移对动物进行预处理。炎性细胞的数量，炎症因子的水平，和肠通透性进行了assessed.ResultsPartial耗尽THERANS与抗CD 25单克隆抗体增强肠通透性诱导IRI。Treg缺失的小鼠显示出更多的中性粒细胞和CD 4 +T细胞。此外，TGFs的耗竭导致肿瘤坏死因子-α、干扰素-γ和白细胞介素（IL）-4的分泌增加，IL-10的水平降低。此外，我们进行了过继转移的Tcl 4，并发现转移Tcl 4显着抑制缺血再灌注引起的肠通透性增加。结论我们的研究表明，Tcl 4参与肠IRI诱导的炎症反应，并以Tcl 4为靶点可能是一种新的治疗方法肠IRI。
BackgroundIschemia-reperfusion injury (IRI) of the intestine is associated with high morbidity and mortality in surgical and trauma patients. T cells participate in the pathogenesis of intestinal IRI, and T-cell depletion has been shown to inhibit inflammatory responses and diminish intestinal damage. However, the mechanism by which T cells contribute to intestinal IRI is not completely understood. Regulatory T cells (Tregs) are a specific subset of T cells that suppress immune responses and protect against tissue injuries. We hypothesized that Tregs might be involved in intestinal IRI.Materials and methodsWe subjected C57/Bl6 mice to 30 min of ischemia by clamping the superior mesenteric artery followed by reperfusion. Animals were pretreated with the anti-CD25 monoclonal antibody or adoptive transfer of Tregs before induction of IRI. The number of inflammatory cells, the level of inflammatory factors, and intestinal permeability were assessed.ResultsPartial depletion of Tregs with an anti-CD25 monoclonal antibody potentiated intestinal permeability induced by IRI. The Treg-depleted mice showed more neutrophils and CD4+T cells. In addition, depletion of Tregs led to enhanced secretion of tumor necrosis factor-α, interferon-gamma, and interleukin (IL)-4 and reduced levels of IL-10. Furthermore, we performed adoptive transfer of Tregs and found that transfer of Tregs significantly inhibited the ischemia-reperfusion–induced increase in intestinal permeability.ConclusionsOur study indicated that Tregs participate in intestinal inflammatory responses induced by IRI and that targeting Tregs could be a novel therapeutic approach to intestinal IRI.