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Trophoblast dysfunction and abnormal macrophage polarization and metabolism are associated with RSA; however, the underlying mechanisms remain unknown. Jupiter microtubule\u2010associated homolog 2 (JPT2) is essential for calcium mobilization; however, its role in RSA remains unclear. In this study, it is found that the expression levels of JPT2, a nicotinic acid adenine dinucleotide phosphate\u2010binding protein, are decreased in the villous tissues of patients with RSA and placental tissues of miscarried mice. Mechanistically, it is unexpectedly found that abnormal JPT2 expression regulates trophoblast function and thus involvement in RSA via c\u2010Jun <jats:italic>N<\/jats:italic>\u2010terminal kinase (JNK) signaling, but not via calcium mobilization. Specifically, on the one hand, JPT2 deficiency inhibits trophoblast adhesion, migration, and invasion by inhibiting the JNK\/atypical chemokine receptor 3 axis. On the other hand, trophoblast JPT2 deficiency contributes to M1 macrophage polarization by promoting the accumulation of citrate and reactive oxygen species via inhibition of the JNK\/interleukin\u20106 axis. Self\u2010complementary adeno\u2010associated virus 9\u2010JPT2 treatment alleviates embryonic resorption in abortion\u2010prone mice. In summary, this study reveals that JPT2 mediates the remodeling of the immune microenvironment at the maternal\u2013fetal interface, suggesting its potential as a therapeutic target for RSA.<\/jats:p>","DOI":"10.1002\/advs.202306359","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T16:30:06Z","timestamp":1709137806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3885-4944","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"first","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development 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