Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion
Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion
复制标题
肠道缺血再灌注后 PD-1 的激活通过 IL-10/miR-155 途径保护肠道免疫防御
DOI：
10.1007/s10620-018-5282-2
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发表时间：
2018-09
影响因子：
3.1
通讯作者：
Liu Zi-Meng
中科院分区：
文献类型：
--
作者：
Zhang Xu-Yu;Guan Su;Zhang Hu-Fei;Li Rui-Yun;Liu Zi-Meng
背景肠缺血再灌注（I/R）后肠免疫球蛋白（IG）功能障碍的机制至今仍不清楚。程序性死亡1（Programmed death 1，PD-1）与淋巴细胞的免疫应答有关，目的探讨PD-1的激活可能通过调节IL-10/miR-155的产生来改善肠缺血再灌注损伤后肠道免疫功能障碍。给予PD-L1融合IG、抗白细胞介素（IL）-10单克隆抗体（mAb）和microRNA（miR）-155阿戈米尔。测量派伊尔集合淋巴结（PP）CD 4+细胞中的PD-1表达、IL-10 mRNA和蛋白表达。分别检测PP组织中miR-155水平、肿瘤坏死因子（TNF）-α和IL-1β浓度以及激活诱导的胞苷脱氨酶（AID）（肠道免疫抗体的关键酶）。重要的是，生产和盲肠的伊加和IgM的细菌结合能力detected.ResultsIntestinal I/R导致PD-1的表达下降，生产不平衡，伊加和IgM的细菌结合能力受损。PD-L1 IG激活PD-1可促进IL-10的合成，降低miR-155水平，促进AID表达，降低TNF-α、IL-1β浓度。AID上调可改善伊加和IgM功能障碍引起的肠道免疫屏障破坏。结论PD-L1 Ig激活PD-1，通过IL-10/miR-155途径减轻肠I/R后肠道免疫防御损伤。PD-1、IL-10和miR-155可能是肠道屏障和免疫损伤的潜在靶点。
BackgroundTo date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes.AimWe aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury.MethodsIntestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer’s patches (PP) CD4+cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1β concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected.ResultsIntestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1β concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense.ConclusionActivation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.
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DOI：
10.1016/j.surge.2012.03.003
发表时间：
2012-12
影响因子：
2.5
作者：
Deitch, Edwin A.
通讯作者：
Deitch, Edwin A.
影响因子：
5
作者：
Fouda AY;Pillai B;Dhandapani KM;Ergul A;Fagan SC
通讯作者：
Fagan SC
影响因子：
7
作者：
Brown KE;Freeman GJ;Wherry EJ;Sharpe AH
通讯作者：
Sharpe AH
DOI：
10.4049/jimmunol.1301810
发表时间：
2013-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Esch KJ;Juelsgaard R;Martinez PA;Jones DE;Petersen CA
通讯作者：
Petersen CA
影响因子：
3.7
作者：
Wang F;Li Q;Wang C;Tang C;Li J
通讯作者：
Li J