Decidual CXCR4(+) CD56(bright) NK cells as a novel NK subset in maternal-foetal immune tolerance to alleviate early pregnancy failure.
Decidual CXCR4(+) CD56(bright) NK cells as a novel NK subset in maternal-foetal immune tolerance to alleviate early pregnancy failure.
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蜕膜 CXCR4( )CD56(bright)NK 细胞作为母胎免疫耐受中的新型 NK 子集，可缓解早期妊娠失败
DOI：
10.1002/ctm2.540
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发表时间：
2021-10
影响因子：
10.6
通讯作者：
Du MR
中科院分区：
文献类型：
--
作者：
Tao Y;Li YH;Zhang D;Xu L;Chen JJ;Sang YF;Piao HL;Jing XL;Yu M;Fu Q;Zhou ST;Li DJ;Du MR
自然杀伤（NK）细胞优先聚集在母胎界面，并被认为在妊娠早期发挥重要的免疫调节作用，相关的免疫功能障碍可能导致妊娠失败，如复发性流产（RM）。然而，建立母胎免疫耐受的机制是复杂的，但澄清蜕膜NK（dNK）细胞的作用提供了设计免疫策略，以帮助RM患者的潜力。在这份报告中，我们分析了RNA测序外周NK细胞（pNK）和蜕膜NK细胞在妊娠早期，我们确定了一个免疫调节dNK亚群CXCR 4 + CD 56 brightdNK和研究其起源和表型和功能特征。相对于CXCR 4阴性亚群，CXCR 4 + CD 56 brightdNK显示出较低的活化和细胞毒性表型，但增强的免疫调节潜力。CXCR 4 + CD 56 brightdNK以IL-4依赖性方式促进Th 2移位，可以从外周血中招募并由滋养细胞重新编程，作为妊娠早期免疫耐受建立的积极参与者。在RM患者和自然流产小鼠模型中发现CXCR 4 + dNK细胞减少及其诱导Th 2分化的能力受损。此外，将CXCR 4 + dNK细胞过继转移至NK缺陷型（Nfil 3-/-）小鼠显示出CXCR 4 + dNK通过恢复Th 2/Th 1偏倚和降低胚胎吸收率的巨大治疗潜力。这种新的dNK细胞亚群的鉴定可能为了解NK细胞在早期妊娠中的作用机制奠定基础，并为RM的诊断和治疗提供潜在的预后因素。蜕膜CXCR 4 + NK细胞亚群从外周血募集并由滋养层细胞重编程。CXCR 4 + dNK细胞具有低活性和低细胞毒性，但诱导Th 2分化能力强的特点，有利于妊娠免疫耐受。CXCR 4 + dNK细胞亚群在流产中减少，并且介导免疫耐受的效力较低。连续转移CXCR 4 + dNK细胞减少妊娠丢失
Natural killer (NK) cells preferentially accumulate at maternal–foetal interface and are believed to play vital immune‐modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal–foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4+CD56brightdNK and investigated its origin and phenotypic and functional characteristics. CXCR4+CD56brightdNK displayed a less activated and cytotoxic phenotype but an enhanced immunomodulatory potential relative to the CXCR4 negative subset. CXCR4+CD56brightdNK promote Th2 shift in an IL‐4‐dependent manner and can be recruited from peripheral blood and reprogramed by trophoblasts, as an active participant in the establishment of immune‐tolerance during early pregnancy. Diminished CXCR4+ dNK cells and their impaired ability to induce Th2 differentiation were found in RM patients and mouse models of spontaneous abortion. Moreover, adoptive transfer of CXCR4+ dNK cells to NK‐deficient (Nfil3–/–) mice showed great therapeutic potential of CXCR4+ dNK via recovering the Th2/Th1 bias and reducing embryo resorption rates. The identification of this new dNK cell subset may lay the foundation for understanding NK cell mechanisms in early pregnancy and provide potential prognostic factors for the diagnosis and therapy of RM. Decidual CXCR4+ NK cell subset is recruited from peripheral blood and reprogramed by trophoblasts. CXCR4+ dNK cells featured with low activity and cytotoxicity but high capacity of inducing Th2 differentiation, are benefit to pregnancy immunotolerance. CXCR4+ dNK cell subset decreases in miscarriage and is less potent to mediate immune tolerance. Adoptive transfer of CXCR4+ dNK cells alleviates pregnancy loss.
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DOI：
10.1146/annurev-pathmechdis-012418-012743
发表时间：
2019-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Deshmukh H;Way SS
通讯作者：
Way SS
NFIL3/E4BP4是在体内开发和成熟所必需的。
DOI：
10.1084/jem.20092176
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kamizono S;Duncan GS;Seidel MG;Morimoto A;Hamada K;Grosveld G;Akashi K;Lind EF;Haight JP;Ohashi PS;Look AT;Mak TW
通讯作者：
Mak TW
影响因子：
7.3
作者：
Jamali, Arezoo;Hadjati, Jamshid;Hartmann, Jessica
通讯作者：
Hartmann, Jessica
DOI：
10.1073/pnas.1206322110
发表时间：
2013-01-15
影响因子：
11.1
作者：
Fu, Binqing;Li, Xianchang;Wei, Haiming
通讯作者：
Wei, Haiming
妊娠早期蜕膜 γ-δ T 细胞通过分泌 IL-10 上调滋养细胞的生物学功能
影响因子：
8.6
作者：
Fan, Deng-Xuan;Duan, Jie;Jin, Li-Ping
通讯作者：
Jin, Li-Ping