Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α.
Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α.
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DOI：
10.1126/scitranslmed.aan2263
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发表时间：
2018-04-25
影响因子：
17.1
通讯作者：
MacKenzie TC
中科院分区：
文献类型：
--
作者：
Frascoli M;Coniglio L;Witt R;Jeanty C;Fleck-Derderian S;Myers DE;Lee TH;Keating S;Busch MP;Norris PJ;Tang Q;Cruz G;Barcellos LF;Gomez-Lopez N;Romero R;MacKenzie TC
健康妊娠是移植物耐受性最成功的形式，而早产（PTL）可能代表母胎耐受性的崩溃。虽然母体免疫反应与妊娠并发症有关，但胎儿对母体抗原的免疫反应通常不被考虑在内。为了在相关的临床环境中检查胎儿免疫系统，我们分析了PTL患者和健康足月对照组的母血和脐带血。我们在这里报道，早产儿的脐带血具有较高的炎症细胞因子和更大的树突状细胞的激活量。此外，早产儿脐带血的特点是存在一群具有1型T辅助表型的中枢记忆细胞，这在足月婴儿中是不存在的，并且母体微嵌合增加。与足月婴儿相比，早产儿的T细胞对母体抗原具有强大的增殖性和促炎反应，但对第三方抗原却没有反应。此外，我们发现来自早产儿的T细胞通过干扰素-γ和肿瘤坏死因子-α刺激子宫肌收缩。同时，我们发现将活化的T细胞过继性直接转移到小鼠胎儿中会导致妊娠丢失。我们的研究结果表明，胎儿对母体抗原的炎症反应和排斥反应可能有助于促进子宫收缩的信号级联反应，胎儿异常的免疫反应应被认为是PTL的发病机制。激活的胎儿T细胞通过诱导母体子宫收缩促进早产。
Healthy pregnancy is the most successful form of graft tolerance, whereas preterm labor (PTL) may represent a breakdown in maternal-fetal tolerance. Although maternal immune responses have been implicated in pregnancy complications, fetal immune responses against maternal antigens are often not considered. To examine the fetal immune system in the relevant clinical setting, we analyzed maternal and cord blood in patients with PTL and healthy term controls. We report here that the cord blood of preterm infants has higher amounts of inflammatory cytokines and a greater activation of dendritic cells. Moreover, preterm cord blood is characterized by the presence of a population of central memory cells with a type 1 T helper phenotype, which is absent in term infants, and an increase in maternal microchimerism. T cells from preterm infants mount a robust proliferative, proinflammatory response to maternal antigens compared to term infants yet fail to respond to third-party antigens. Furthermore, we show that T cells from preterm infants stimulate uterine myometrial contractility through interferon-γ and tumor necrosis factor–α. In parallel, we found that adoptive transfer of activated T cells directly into mouse fetuses resulted in pregnancy loss. Our findings indicate that fetal inflammation and rejection of maternal antigens can contribute to the signaling cascade that promotes uterine contractility and that aberrant fetal immune responses should be considered in the pathogenesis of PTL. Activated fetal T cells promote preterm labor through the induction of maternal uterine contractions.
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DOI：
10.4049/jimmunol.1502587
发表时间：
2016-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Frascoli M;Jeanty C;Fleck S;Moradi PW;Keating S;Mattis AN;Tang Q;MacKenzie TC
通讯作者：
MacKenzie TC
影响因子：
82.9
作者：
Gibbons, Deena;Fleming, Paul;Hayday, Adrian
通讯作者：
Hayday, Adrian
影响因子：
82.9
作者：
Huang B;Faucette AN;Pawlitz MD;Pei B;Goyert JW;Zhou JZ;El-Hage NG;Deng J;Lin J;Yao F;Dewar RS 3rd;Jassal JS;Sandberg ML;Dai J;Cols M;Shen C;Polin LA;Nichols RA;Jones TB;Bluth MH;Puder KS;Gonik B;Nayak NR;Puscheck E;Wei WZ;Cerutti A;Colonna M;Chen K
通讯作者：
Chen K
影响因子：
20.3
作者：
Bunders, Madeleine J.;van der Loos, Chris M.;Kuijpers, Taco W.
通讯作者：
Kuijpers, Taco W.
DOI：
10.1038/nri2873
发表时间：
2010-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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