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Inadequate placental perfusion has been closely associated with several pregnancy-associated diseases. Galectin-9 (Gal-9) has a wide variety of regulatory functions in innate and adaptive immunity during infection, tumor growth, and organ transplantation. We utilized immortalized human first-trimester extravillous trophoblast cells (HTR8\/SVneo) for our functional study and examined the effects of Gal-9 on apoptosis, cytokine production and angiogenesis of HTR8\/SVneo cells. Gal-9 inhibited the apoptosis and IFN-\u03b3 and IL-17A production, promoted IL-4 production, and coordinated the crosstalk between HTR8\/SVneo cells and human umbilical vein endothelial cells via its interaction with Tim-3. Blockade of JNK signaling inhibited Gal-9 activities in HTR8\/SVneo cells. In addition, we detected a correlation between low levels of Gal-9 and spontaneous abortion. So Gal-9 could inhibit the apoptosis and proinflammatory cytokine expression, and promote the angiogenesis and IL-4 production in HTR8\/SVneo cells via Tim-3 in a JNK dependent manner to help the maintenance of normal pregnancy. These findings possibly identify Gal-9 as a key regulator of trophoblast cells and suggest its potential as a biomarker and target for the treatment of recurrent pregnancy loss.<\/jats:p>","DOI":"10.1530\/rep-19-0543","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T08:58:32Z","timestamp":1601629112000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":15,"title":["Galectin-9 regulates HTR8\/SVneo function via JNK signaling"],"prefix":"10.1093","volume":"161","author":[{"given":"Mengdie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology , Guangzhou First People\u2019s Hospital, School of Medicine, South China University of Technology, Guangzhou, China"},{"name":"Laboratory for Reproductive Immunology , NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China"},{"name":"Department of Gynecology , Jing\u2019an District Central Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiandong","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology , NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Qian","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology , NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female 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