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Open AccessArticle

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

1
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, University of Florence, 50134 Florence, Italy
2
Department of Gynecology and Obstetrics, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia
3
Immunology Area, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy
4
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 428; https://doi.org/10.3390/ijms20020428
Received: 18 December 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 19 January 2019
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology)
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-γ 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. View Full-Text
Keywords: Th22; Th17; pregnancy; IL-22; IL-4; IL-5; IL-17; spontaneous abortion; ectopic pregnancy; implantation Th22; Th17; pregnancy; IL-22; IL-4; IL-5; IL-17; spontaneous abortion; ectopic pregnancy; implantation
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Logiodice, F.; Lombardelli, L.; Kullolli, O.; Haller, H.; Maggi, E.; Rukavina, D.; Piccinni, M.-P. 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. Int. J. Mol. Sci. 2019, 20, 428.

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