{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:44:05Z","timestamp":1792802645290,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T00:00:00Z","timestamp":1597449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>The balance of the immune microenvironment along the maternal\u2010fetal interface is closely related to pregnancy outcomes, with excessive inflammatory reactions leading to the occurrence of pathological pregnancy outcomes such as abortion. CaMK4 has been reported to play a significant role in autoimmune diseases through the regulation of Th17 cells. However, whether CaMK4 is associated with spontaneous abortion or the immune microenvironment along the maternal\u2010fetal interface remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods of study<\/jats:title><jats:p>In this study, we constructed normal pregnancy and LPS\u2010induced abortion models in mice, and a CaMK4 inhibitor called KN\u201093 was administered to investigate the changes in and mechanisms of the immune response. The expression of CaMK4 was evaluated in the uteroplacental complex and spleen. Furthermore, the infiltration and function of Th17 cells were estimated in peripheral tissues and the uteroplacental complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of CaMK4 in the uteroplacental complex and spleen was significantly higher in the LPS\u2010treated group than in the normal pregnancy group. KN\u201093, the CaMK4 inhibitor, reversed fetal resorption and excessive inflammation. In detail, KN\u201093 led to reduced infiltration of Th17 cells into peripheral tissues and the uteroplacental complex, and the functions of Th17 cells were inhibited. In addition, CaMK4 promoted the AKT\/mTOR signaling pathway, which is one of the mechanisms that regulate the immune microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CaMK4 is a critical regulator that promotes the expansion of Th17 cells and enhances their functions through the AKT\/mTOR signaling pathway. The inhibition of CaMK4 can reverse the immune imbalance along the maternal\u2010fetal interface and improve pregnancy outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13315","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T17:29:08Z","timestamp":1596302948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CaMK4 promotes abortion\u2010related Th17 cell imbalance by activating AKT\/mTOR signaling pathway"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7279-1556","authenticated-orcid":false,"given":"Shuo","family":"Chang","sequence":"first","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development Wuhan 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