{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:49Z","timestamp":1787028409550,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,19]],"date-time":"2019-01-19T00:00:00Z","timestamp":1547856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European NoE EMBIC","award":["LSHM-CT-2004-512040"],"award-info":[{"award-number":["LSHM-CT-2004-512040"]}]},{"name":"Intramural Scientific Research (ex-60%) of the University of Florence","award":["RICATEN18"],"award-info":[{"award-number":["RICATEN18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Trophoblast expressing paternal HLA-C resembles a semiallograft, and could be rejected by maternal T cells. IL-22 seems to be involved in allograft rejection and thus could be responsible for miscarriages. We examined the role of decidual IL-22-producing CD4+ T on human pregnancy. In those experiencing successful pregnancy and those experiencing unexplained recurrent abortion (URA), the levels of IL-22 produced by decidual CD4+ T cells are higher than those of peripheral blood T cells. We found a correlation of IL-22 and IL-4 produced by decidual CD4+ T cells in those experiencing successful pregnancy, not in those experiencing URA. The correlation of IL-22 and IL-4 was also found in the serum of successful pregnancy. A prevalence of CD4+ T cells producing IL-22 and IL-4 (Th17\/Th2\/IL-22+, Th17\/Th0\/IL-22+, Th17\/Th2\/IL-22+, and Th0\/IL-22+ cells) was observed in decidua of those experiencing successful pregnancy, whereas Th17\/Th1\/IL-22+ cells, which do not produce IL-4, are prevalent in those experiencing URA. Th17\/Th2\/IL-22+ and Th17\/Th0\/IL-22+ cells are exclusively present at the embryo implantation site where IL-4, GATA-3, IL-17A, ROR-C, IL-22, and AHR mRNA are expressed. T-bet and IFN-\u03b3 mRNA are found away from the implantation site. There is no pathogenic role of IL-22 when IL-4 is also produced by decidual CD4+ cells. Th17\/Th2\/IL-22+ and Th17\/Th0\/IL-22+ cells seem to be crucial for embryo implantation.<\/jats:p>","DOI":"10.3390\/ijms20020428","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T03:08:22Z","timestamp":1548126502000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Decidual Interleukin-22-Producing CD4+ T Cells (Th17\/Th0\/IL-22+ and Th17\/Th2\/IL-22+, Th2\/IL-22+, Th0\/IL-22+), Which Also Produce IL-4, Are Involved in the Success of Pregnancy"],"prefix":"10.3390","volume":"20","author":[{"given":"Federica","family":"Logiodice","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Lombardelli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornela","family":"Kullolli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy"},{"name":"Immunology Area, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rukavina","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-5209","authenticated-orcid":false,"given":"Marie-Pierre","family":"Piccinni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1053\/plac.1999.0496","article-title":"Surface expression of HLA-C antigen by human extravillous trophoblast","volume":"21","author":"King","year":"2000","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/eji.201470065","article-title":"Medawar and the immunological paradox of pregnancy: 60 years on","volume":"44","author":"Colucci","year":"2014","journal-title":"Eur. 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