{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:44:26Z","timestamp":1773924266261,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China (NSFC)","award":["31770989"],"award-info":[{"award-number":["31770989"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Decidual natural killer cells (dNK cells) are an essential component of the immune cells present at the maternal\u2013foetal interface during early pregnancy, and they play a vital role in various physiological processes. Abnormalities in the ratio or function of dNK cells have been linked to recurrent miscarriages. CD96 has been previously shown to regulate NK cell function in the tumour microenvironment; however, its role and mechanism at the maternal\u2013foetal interface remains unclear. The present study aimed to investigate the immunomodulatory role of CD96 in dNK cells and its function at the maternal\u2013foetal interface. Immunofluorescence staining and flow cytometry were used to detect the expression of cellular markers such as CD96. Furthermore, the secretory function, adhesion-function-related molecules, and cell proliferation markers of CD96+ and CD96\u2212 dNK cells were detected using flow cytometry. In addition, we performed cell culture experiments via the magnetic bead sorting of NK cells to detect changes in the expression of the aforementioned functional molecules in dNK cells after the CD96 blockade. Furthermore, we examined the functional characteristics of dNK cells after palmitic acid treatment at a concentration of 10 \u03bcM. We also examined the changes in dNK cell function when subjected to the combined effect of palmitic acid and CD96 antagonists. The results indicated that CD96, TIGIT, CD155, and CD112 were highly expressed at the maternal\u2013foetal interface, with dNK cells predominantly expressing CD96, whereas TIGIT was mainly expressed on T cells, and CD155 and CD112 were mainly present in metaphase stromal and trophoblast cells. CD96+ dNK cells displayed low cytotoxic activity and a high adhesion phenotype, which mediated the immunosuppressive effect on dNK cells at the maternal\u2013foetal interface. Palmitic acid upregulated CD96 expression on the surface of dNK cells in the coculture system, inhibiting dNK cell activity and increasing their adhesion molecule expression. CD96 antagonist treatment blocked the inhibitory effect of trophoblasts on dNK cells, resulting in enhanced cytokine secretion and reduced adhesion. The results of this study provide valuable insight into the immunomodulatory role of CD96 in dNK cells and its mechanism at the maternal\u2013foetal interface, particularly in metaphase NK cells. This study sheds light on the mechanisms of immune regulation at the maternal\u2013foetal interface and their implications for the study of recurrent miscarriages of unknown origin.<\/jats:p>","DOI":"10.3390\/bioengineering10091008","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:25:33Z","timestamp":1692951933000},"page":"1008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Palmitic Acid Upregulates CD96 Expression to Mediate Maternal\u2013Foetal Interface Immune Tolerance by Inhibiting Cytotoxic Activity and Promoting Adhesion Function in Human Decidual Natural Killer Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-6644","authenticated-orcid":false,"given":"Yingjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Assisted Reproduction, School of Medicine, Shanghai Ninth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University, No. 500 Zhizaoju Road, Huangpu District, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, School of Medicine, Shanghai Ninth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University, No. 500 Zhizaoju Road, Huangpu District, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","first-page":"6247526","article-title":"Human Uterine Decidual NK Cells in Women with a History of Early Pregnancy Enhance Angiogenesis and Trophoblast Invasion","volume":"2020","author":"Jia","year":"2020","journal-title":"BioMed Res. 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