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In this study, we observed higher levels of receptor activator for nuclear factor-\u03ba B ligand (RANKL) on decidual stromal cells (DSCs), and its receptor RANK on d\u03b3\u03b4\u03a4 cells in decidua from normal pregnancy compared with patients with recurrent spontaneous abortion (RSA). RANKL expressed by DSCs can induce the polarization of peripheral blood \u03b3\u03b4\u03a4 (p\u03b3\u03b4\u03a4) and d\u03b3\u03b4\u03a4 cells to Foxp3\u2009+\u2009\u03b3\u03b4\u03a4 cells, and upregulate the expression of transforming growth factor (TGF)-\u03b21. This process is mediated through activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB). In addition, RANKL promotes the adhesion of d\u03b3\u03b4\u03a4 cells to DSCs in vitro, which is associated with the upregulation of ICAM-1 and VCAM-1 on DSCs and integrins on d\u03b3\u03b4\u03a4 cells. RANKL knockout leads to the decreased numbers of uterus total \u03b3\u03b4\u03a4 cells, Foxp3+\u03b3\u03b4\u03a4 cells and the expression of TGF-\u03b21, and the increased pregnancy loss in mice. These results suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by triggering the polarization and residence of TGF-\u03b21-producing Foxp3+\u03b3\u03b4\u03a4 cells in early pregnancy. The abnormal low level of RANKL\/RANK results in pregnancy loss because of the dialogue disorder between DSCs and d\u03b3\u03b4\u03a4 cells. This observation provides a scientific basis on which a potential marker can be detected to early warning of pregnancy loss.<\/jats:p>","DOI":"10.1038\/s41419-019-1380-0","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T13:31:59Z","timestamp":1549632719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Decidual RANKL\/RANK interaction promotes the residence and polarization of TGF-\u03b21-producing regulatory \u03b3\u03b4 T cells"],"prefix":"10.1038","volume":"10","author":[{"given":"Rui-Qi","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Han","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3759-1030","authenticated-orcid":false,"given":"Ming-Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,8]]},"reference":[{"key":"1380_CR1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.it.2018.01.007","volume":"39","author":"JZ Zhou","year":"2018","unstructured":"Zhou, J. 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