Zhang Xu-Yu, Liu Zi-Meng, Zhang Hu-Fei, Li Yun-Sheng, Wen Shi-Hong, Shen Jian-Tong, Liu Ke-Xuan
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
Dig Dis Sci. 2015 Sep;60(9):2662-9. doi: 10.1007/s10620-015-3684-y. Epub 2015 May 6.
Intestinal ischemia/reperfusion (I/R) disrupts intestinal mucosal integrity and immunoglobulin A (IgA) generation. It has recently been shown that the programmed cell death-1 receptor (PD-1) plays a crucial role in regulating intestinal secreted IgA (sIgA).
To evaluate changes in PD-1 and PD-ligand 1 (PD-L1) expression on Peyer's patches (PP) CD4(+) T cells and to investigate the correlation between PD-1/PD-L1 and intestinal IgA production/mucosal integrity in mice following intestinal I/R.
I/R injury was induced by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-1/PD-L1 expression on PP CD4(+) T cells was measured in I/R and sham-operated mice. Additionally, transforming growth factor-β1 (TGF-β1) and interleukin-21 (IL-21) mRNA in CD4(+) T cells and IgA(+) and IgM(+) in PP B cells, as well as intestinal mucosal injury and sIgA levels, were assessed.
PD-1/PD-L1, TGF-β1, and IL-21 expression was down-regulated after intestinal I/R. Furthermore, IgA(+) B cells decreased and IgM(+) B cells increased in mice with intestinal I/R. Importantly, decreased PD-1/PD-L1 expression was correlated with increased mucosal injury and decreased IgA levels, as well as with decreased TGF-β1 and IL-21 expression.
Intestinal I/R inhibits PD-1/PD-L1 expression on PP CD4(+) T cells, which was associated with an impaired intestinal immune system and mechanical barriers. Our study indicates that PD-1/PD-L1 expression on CD4(+) T cells may be involved in the pathogenesis of intestinal I/R injury.
肠道缺血/再灌注（I/R）会破坏肠道黏膜完整性并影响免疫球蛋白A（IgA）的产生。最近研究表明，程序性细胞死亡蛋白1受体（PD-1）在调节肠道分泌型IgA（sIgA）中起关键作用。
评估派尔集合淋巴结（PP）CD4(+) T细胞上PD-1和程序性死亡受体配体1（PD-L1）表达的变化，并研究肠道I/R后小鼠体内PD-1/PD-L1与肠道IgA产生及黏膜完整性之间的相关性。
通过夹闭肠系膜上动脉1小时然后再灌注2小时诱导I/R损伤。检测I/R小鼠和假手术小鼠PP CD4(+) T细胞上的PD-1/PD-L1表达。此外，评估CD4(+) T细胞中转化生长因子-β1（TGF-β1）和白细胞介素-21（IL-21）的信使核糖核酸（mRNA）水平、PP B细胞中IgA(+)和IgM(+)水平，以及肠道黏膜损伤和sIgA水平。
肠道I/R后，PD-1/PD-L1、TGF-β1和IL-21的表达下调。此外，肠道I/R小鼠中IgA(+) B细胞减少而IgM(+) B细胞增加。重要的是，PD-1/PD-L1表达降低与黏膜损伤增加、IgA水平降低以及TGF-β1和IL-21表达降低相关。
肠道I/R抑制PP CD4(+) T细胞上PD-1/PD-L1的表达，这与肠道免疫系统和机械屏障受损有关。我们的研究表明，CD4(+) T细胞上的PD-1/PD-L1表达可能参与肠道I/R损伤的发病机制。
