近日來自中國科技大學(xué)的研究人員在《美國科學(xué)院院刊》（PNAS）上發(fā)表了題為“Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface ”的研究論文,，解析了自然殺傷（NK）細(xì)胞在胚胎耐受中的功能及作用機(jī)制,。
中國科技大學(xué)生命科學(xué)學(xué)院的魏海明（Haiming Wei）教授和田志剛( Zhigang Tian)教授是這篇論文的共同通訊作者,。前者的主要研究興趣是NK細(xì)胞亞群與重要疾病發(fā)生發(fā)展的關(guān)系,；基于天然免疫的腫瘤生物治療技術(shù),。后者主要從事天然免疫與重要疾病機(jī)理及其相關(guān)生物治療技術(shù)與產(chǎn)品的應(yīng)用基礎(chǔ)研究,。
妊娠是一個(gè)復(fù)雜的生理過程,，從免疫學(xué)角度看類似于器官移植,。帶有父方異體抗原成分的胚胎,，對(duì)于母體來說是一個(gè)移植物,，母體免疫系統(tǒng)對(duì)此進(jìn)行識(shí)別，并產(chǎn)生免疫應(yīng)答,；但就其結(jié)局而言又與器官移植不同,，正常狀態(tài)下，母體對(duì)于胎兒并不產(chǎn)生排斥,，而是產(chǎn)生保護(hù)性免疫應(yīng)答,。
NK 細(xì)胞是天然免疫系統(tǒng)的重要成員,分布于外周各淋巴器官及血液循環(huán)系統(tǒng)。不同與T,、B細(xì)胞,NK細(xì)胞無需抗原的預(yù)先刺激與活化即可發(fā)揮細(xì)胞毒效應(yīng),并分泌多種細(xì)胞因子及趨化因子,具有殺傷微生物及招募免疫系統(tǒng)中其他細(xì)胞等多種生物學(xué)功能,從而在抗擊感染,自身免疫病及腫瘤等多種疾病中發(fā)揮重要功能,。近期越來越多的研究發(fā)現(xiàn),NK細(xì)胞除殺傷腫瘤的能力外,更具有調(diào)節(jié)免疫系統(tǒng)和維持免疫平衡的功能,。尤其是在妊娠早期,超過80%的母胎界面淋巴細(xì)胞均為NK細(xì)胞,而其免疫學(xué)功能至今不為人知。
在這篇文章中,，研究人員發(fā)現(xiàn)在妊娠過程中,，母-胎界面存在炎性TH17細(xì)胞，并出現(xiàn)了局部炎癥,。蛻膜NK細(xì)胞可以通過抑制炎性TH17細(xì)胞,維持母胎耐受和免疫平衡,，并且這一過程是通過CD56brightCD27+NK細(xì)胞所分泌的IFN-γ和IL-1RA等細(xì)胞因子實(shí)現(xiàn)的。這種NK細(xì)胞介導(dǎo)的調(diào)控性反應(yīng)在反復(fù)自然流產(chǎn)的患者中喪失,，促進(jìn)了TH17細(xì)胞極化,，導(dǎo)致炎癥加劇,；這一局部炎癥反應(yīng)進(jìn)一步影響了NK細(xì)胞的調(diào)控功能,，導(dǎo)致母胎耐受平衡被打破,造成妊娠失敗。
新研究證實(shí)NK細(xì)胞作為調(diào)節(jié)性細(xì)胞抑制了TH17介導(dǎo)的炎性反應(yīng),，維持了耐受平衡,，從而保障了妊娠正常進(jìn)行。這對(duì)更好的理解NK細(xì)胞的調(diào)節(jié)功能,深入研究胚胎耐受的機(jī)理有重要意義,。(生物谷Bioon.com)
doi: 10.1073/pnas.1206322110
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Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface
Binqing Fua, Xianchang Lib,c, Rui Suna, Xianhong Tongd, Bin Lingd, Zhigang Tiana,1, and Haiming Weia,1
Natural killer (NK) cells accumulate at the maternal–fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that TH17 cells and local inflammation can occur at the maternal–fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory TH17 cells via IFN-γ secreted by the CD56brightCD27+ NK subset. This NK-cell–mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent TH17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal–fetal interface by suppressing TH17-mediated local inflammation.
