Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal-Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells
Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal-Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells
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胚胎滋养层通过胸腺基质淋巴细胞生成素指导树突状细胞诱导蜕膜调节性 T 细胞分化和母婴耐受
DOI：
10.4049/jimmunol.1203425
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发表时间：
2014-02-15
影响因子：
4.4
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Du, Mei-Rong;Guo, Pei-Fen;Li, Da-Jin
生理妊娠需要母体免疫系统识别和耐受胚胎抗原。虽然已经提出了多种机制，但目前尚不清楚胎儿如何逃避母体免疫系统。在这篇文章中，我们证明了滋养层细胞来源的胸腺基质淋巴细胞生成素（TSLP）指示蜕膜CD 11 c+树突状细胞（dDCs）增加共刺激分子，MHC II类，和Th 2/3型，但不是Th 1型，细胞因子。TSLP激活的dDC通过TGF-β1诱导蜕膜CD 4 + CD 25 − T细胞增殖和分化为CD 4 + CD 25 + FOXP 3+调节性T细胞（TCRs）。TSLP激活的dDC诱导的TcR显示免疫抑制特征并表达Th 2型细胞因子。此外，蜕膜CD 4 + CD 25 + FOXP 3 + T细胞因子促进滋养层细胞的侵袭性和HLA-G表达，导致优先产生Th 2细胞因子，并降低蜕膜CD 56 brightCD 16 − NK细胞的细胞毒性。有趣的是，在流产期间，在母胎界面观察到TSLP表达减少和THBE数量减少。我们的研究确定了一个新的反馈回路之间的胚胎来源的滋养层细胞和母体蜕膜白细胞，诱导耐受性免疫反应，以确保成功怀孕。
Physiological pregnancy requires the maternal immune system to recognize and tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is not yet clear how the fetus evades the maternal immune system. In this article, we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP) instructs decidual CD11c+ dendritic cells (dDCs)with increased costimulatory molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines. TSLP-activated dDCs induce proliferation and differentiation of decidual CD4+CD25− T cells into CD4+CD25+FOXP3+ regulatory T cells (Tregs) through TGF-β1. TSLP-activated dDC–induced Tregs display immunosuppressive features and express Th2-type cytokines. In addition, decidual CD4+CD25+FOXP3+ Tregs promote invasiveness and HLA-G expression of trophoblasts, resulting in preferential production of Th2 cytokines and reduced cytotoxicity in decidual CD56brightCD16− NK cells. Of interest, decreased TSLP expression and reduced numbers of Tregs were observed at the maternal–fetal interface during miscarriage. Our study identifies a novel feedback loop between embryo-derived trophoblasts and maternal decidual leukocytes, which induces a tolerogenic immune response to ensure a successful pregnancy.