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However, uncontrolled TLR-triggered inflammation will endanger normal pregnancy, resulting in pregnancy loss. Therefore, maintenance of a moderate inflammatory response is crucial for successful pregnancy under conditions of infection. Here, we demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play important roles in maintaining successful pregnancies. Activation of TLR signaling induced pro-inflammatory cytokine production and apoptosis of DSCs, which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected DSCs from TLR-mediated apoptosis in an ERK1\/2 pathway-dependent manner. In addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production by DSCs through suppressing NF-\u03baB activation. Tim-3 increased production of T helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS on Th2 cytokine generation by up-regulation of interferon regulatory factor 4 expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory response to LPS stimulation. Thus, Tim-3 signaling could represent a \u201cself-control\u201d mechanism in TLR-triggered inflammation during pregnancy. These findings identify Tim-3 as a key regulator of DSCs and suggest its potential as a target for the treatment of spontaneous abortion.<\/jats:p>","DOI":"10.1038\/srep09013","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T10:48:24Z","timestamp":1426070904000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface"],"prefix":"10.1038","volume":"5","author":[{"given":"SongCun","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ChunMei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HaiLan","family":"Piao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YanHong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XiaoMing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MinMin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DaJin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MeiRong","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,3,11]]},"reference":[{"key":"BFsrep09013_CR1","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1056\/NEJMcp1005330","volume":"363","author":"DW Branch","year":"2010","unstructured":"Branch, D. 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