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The aim of the study was to assess the binding of gp96 to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a+ DCs present at the maternal-fetal interface in vitro as well as the influence of CD1a+ DCs maturation status. Immunohistology and immunofluorescence of paraffin-embedded first-trimester decidua tissue sections of normal and pathological (missed abortion MA and blighted ovum BO) pregnancies were performed together with flow cytometry detection of antigens in CD1a+ DCs after gp96 stimulation of decidual mononuclear cells. Gp96 efficiently bound CD91 and TLR4 receptors on decidual CD1a+ DCs in a dose-dependent manner and increased the expression of CD83 and HLA-DR. The highest concentration of gp96 (1000 ng\/mL) increased the percentage of Interferon-\u03b3 (INF-\u03b3) and IL-15 expressing gp96+ cells. Gp96 binds CD91 and TLR4 on decidual CD1a+ DCs, which causes their maturation and significantly increases INF-\u03b3 and IL-15 in the context of Th1 cytokine\/chemokine domination, which could support immune response harmful for ongoing pregnancy.<\/jats:p>","DOI":"10.3390\/ijms24032278","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:29:45Z","timestamp":1674523785000},"page":"2278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Human Decidual CD1a+ Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-1728","authenticated-orcid":false,"given":"Tamara","family":"Gulic","sequence":"first","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordana","family":"Laskarin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Glavan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Clinical Hospital Rijeka, University of Rijeka, Kresimirova 42a, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-5263","authenticated-orcid":false,"given":"Tanja","family":"Grubi\u0107 Kezele","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia"},{"name":"Department of Microbiology, Clinical Hospital Rijeka, University of Rijeka, Kresimirova 42a, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Clinical Hospital Rijeka, University of Rijeka, Kresimirova 42a, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Rukavina","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia"},{"name":"Department of Biomedical Sciences in Rijeka, Croatian Academy of Sciences and Arts, R. Matej\u010di\u0107 2, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1600-0897.2008.00619.x","article-title":"Distribution and maturity of dendritic cells in diseases of insufficient placentation","volume":"60","author":"Scholz","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.mehy.2010.07.023","article-title":"Regulation of NK-cell function by mucins via antigen-presenting cells","volume":"75","author":"Laskarin","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_3","first-page":"458","article-title":"Extravillous trophoblast and decidual natural killer cells: A remodelling partnership","volume":"18","author":"Alison","year":"2012","journal-title":"Hum. 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