胎儿胎盘细胞外囊泡将孕源性抗原传递到母体二级淋巴组织进行免疫识别。

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Juliana S Powell, Adriana T Larregina, William J Shufesky, Mara Lg Sullivan, Donna Beer Stolz, Stephen J Gould, Geoffrey Camirand, Sergio D Catz, Simon C Watkins, Yoel Sadovsky, Adrian E Morelli
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引用次数: 0

摘要

妊娠是一个免疫学悖论,尽管母体免疫系统有能力,但在胎胎盘界面和母体次级淋巴组织(slt)的调节机制规避了对半同种异体概念的排斥。小细胞外囊泡(sev)是细胞间通讯的载体;然而,胎儿胎盘sev在抗原转运到母体slt中的作用尚未得到最终证实。在小鼠实验中,孕鼠产生的含氟探针标记的sev通过质膜脱落或从内噬室释放,我们发现胎胎盘sev被递送到母体脾脏的免疫细胞中。注射从Act-mOVA B6雄性胚胎受精的雌性胎盘中提取的sev,在未受精的雌性胚胎中引起ova特异性CD8+ OT-I T细胞在怀孕期间的次优激活。此外,当OVA+卵缺乏sEV分泌所需的蛋白Rab27a时,母体脾脏中OT-I细胞的增殖能力下降。蛋白质组学分析显示,小鼠滋养细胞sev富含抗炎和免疫抑制介质。用人滋养细胞培养物的sev注射人源化小鼠,测试了翻译相关性。我们的研究结果表明,sev将胎儿胎盘抗原传递给母体T细胞识别的slt。这种机制的改变可能导致妊娠障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fetoplacental extracellular vesicles deliver conceptus-derived antigens to maternal secondary lymphoid tissues for immune recognition.

Pregnancy is an immunological paradox where despite a competent maternal immune system, regulatory mechanisms at the fetoplacental interface and maternal secondary lymphoid tissues (SLTs) circumvent rejection of semi-allogeneic concepti. Small extracellular vesicles (sEVs) are a vehicle for intercellular communication; nevertheless, the role of fetoplacental sEVs in transport of antigens to maternal SLTs has not been conclusively demonstrated. Using mice in which the conceptus generates fluoroprobe-tagged sEVs shed by the plasma membrane or released from the endocytic compartment, we show that fetoplacental sEVs are delivered to immune cells in the maternal spleen. Injection of sEVs from placentas of females impregnated with Act-mOVA B6 males elicited suboptimal activation of OVA-specific CD8+ OT-I T cells in virgin females as occurs during pregnancy. Furthermore, when OVA+ concepti were deficient in Rab27a, a protein required for sEV secretion, OT-I cell proliferation in the maternal spleen was decreased. Proteomics analysis revealed that mouse trophoblast sEVs were enriched in antiinflammatory and immunosuppressive mediators. Translational relevance was tested in humanized mice injected using sEVs from cultures of human trophoblasts. Our findings show that sEVs deliver fetoplacental antigens to the mother's SLTs that are recognized by maternal T cells. Alterations of such a mechanism may lead to pregnancy disorders.

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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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