Expression of Immune Checkpoint Receptors in Placentae With Infectious and Non-Infectious Chronic Villitis.
Expression of Immune Checkpoint Receptors in Placentae With Infectious and Non-Infectious Chronic Villitis.
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免疫检查点受体在感染性和非感染性慢性绒毛炎胎盘中的表达
DOI：
10.3389/fimmu.2021.705219
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发表时间：
2021
影响因子：
7.3
通讯作者：
Enninga EAL
中科院分区：
文献类型：
--
作者：
Shahi M;Mamber Czeresnia R;Cheek EH;Quinton RA;Chakraborty R;Enninga EAL
妊娠是一种免疫学悖论，母体免疫接受遗传独特的胎儿（或胎儿），同时保持对感染性病原体的保护性先天和适应性反应。这种遗传多样性的母亲和胎儿之间的密切接触需要滋养层细胞信号启动的免疫耐受的许多机制。然而，在一种被称为病因不明的绒毛炎（VUE）的胎盘疾病中，这种耐受性似乎被破坏，允许母体细胞毒性T细胞进入胎盘以破坏胎儿绒毛。VUE与几种妊娠并发症有关，并增加了随后妊娠复发的风险，使其成为重要的产科诊断。VUE的病因尚不清楚，但通过免疫检查点途径的功能失调信号可能发挥着重要作用，该途径在削弱免疫反应方面发挥着关键作用。因此，使用来自正常妊娠（n=8）、VUE（n=8）和巨细胞病毒（CMV）感染的胎盘（n=4）的胎盘组织，我们旨在通过免疫组织化学（IHC）鉴定这些病因之间程序性细胞死亡1（PD-1）、程序性死亡配体-1（PD-L1）、LAG 3和CTLA 4表达的差异。结果表明，与对照和CMV感染相比，VUE胎盘滋养层细胞上的PD-L1表达显著降低。此外，与感染和对照相比，我们观察到在VUE期间浸润到绒毛中的PD-1+（>100个细胞/图像）和LAG 3+（0-120个细胞/图像）细胞的计数显著更高。在所有胎盘中观察到最小CTLA 4染色，仅少数Hofbauer细胞染色阳性。总之，这表明通过免疫检查点信号传导的耐受性丧失可能是导致VUE期间母体细胞活化和运输到胎儿绒毛中的重要机制。进一步的机制研究是必要的，以了解可能的同种异体移植排斥反应更清楚，并制定有效的策略，以防止这种情况发生在子宫内。
Pregnancy is an immunological paradox whereby maternal immunity accepts a genetically unique fetus (or fetuses), while maintaining protective innate and adaptive responses to infectious pathogens. This close contact between the genetically diverse mother and fetus requires numerous mechanisms of immune tolerance initiated by trophoblast cell signals. However, in a placental condition known as villitis of unknown etiology (VUE), there appears to be a breakdown in this tolerance allowing maternal cytotoxic T-cells to traffic into the placenta to destroy fetal villi. VUE is associated with several gestational complications and an increased risk of recurrence in a subsequent pregnancy, making it a significant obstetrical diagnosis. The cause of VUE remains unclear, but dysfunctional signaling through immune checkpoint pathways, which have a critical role in blunting immune responses, may play an important role. Therefore, using placental tissue from normal pregnancy (n=8), VUE (n=8) and cytomegalovirus (CMV) infected placentae (n=4), we aimed to identify differences in programmed cell death 1 (PD-1), programmed death ligand-1 (PD-L1), LAG3 and CTLA4 expression between these etiologies by immunohistochemistry (IHC). Results demonstrated significantly lower expression of PD-L1 on trophoblast cells from VUE placentae compared to control and CMV infection. Additionally, we observed significantly higher counts of PD-1+ (>100 cells/image) and LAG3+ (0-120 cells/image) cells infiltrating into the villi during VUE compared to infection and control. Minimal CTLA4 staining was observed in all placentae, with only a few Hofbauer cells staining positive. Together, this suggests that a loss of tolerance through immune checkpoint signaling may be an important mechanism leading to the activation and trafficking of maternal cells into fetal villi during VUE. Further mechanistic studies are warranted to understand possible allograft rejection more clearly and in developing effective strategies to prevent this condition from occurring in utero.
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影响因子：
9.8
作者：
Althaus, J;Weir, EG;Blakemore, K
通讯作者：
Blakemore, K
影响因子：
3.8
作者：
Benirschke, K;Coen, R;Key, T
通讯作者：
Key, T
影响因子：
3.8
作者：
Egal, E. S. A.;Mariano, F. V.;Altemani, A. M.
通讯作者：
Altemani, A. M.
影响因子：
1.9
作者：
Ernst, LM;Crouch, J;Howe, JG
通讯作者：
Howe, JG
DOI：
10.1084/jem.20160801
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Juneja VR;McGuire KA;Manguso RT;LaFleur MW;Collins N;Haining WN;Freeman GJ;Sharpe AH
通讯作者：
Sharpe AH