At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success
We investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human trophoblast cells produced IL-...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4926 |
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| author | Letizia Lombardelli Federica Logiodice Ornela Kullolli Herman Haller Chiara Agostinis Roberta Bulla Daniel Rukavina Marie-Pierre Piccinni |
| author_facet | Letizia Lombardelli Federica Logiodice Ornela Kullolli Herman Haller Chiara Agostinis Roberta Bulla Daniel Rukavina Marie-Pierre Piccinni |
| author_sort | Letizia Lombardelli |
| collection | DOAJ |
| description | We investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human trophoblast cells produced IL-35 but not IL-4 or IL-10. RhIL-35, at concentrations produced by human trophoblasts, polarized T cells towards IL-35+, IL-10+, IL-4+ Th2-type cells and to Foxp3+ EBI3+ p35+ T reg cells producing IL-35 but not IL-10 and IL-4. Moreover, rhIL-35 at low concentrations did not suppress the proliferation of Th cells but stimulated IL-4 and IL-10 production by established Th clones. In particular, Th1-type clones acquired the capacity to produce IL-4. In addition, purified human trophoblast cell supernatants containing IL-35 upregulated IL-4 and IL-10 production by Th clones. Finally, IL-35+, IL-10+, IL-4+ Th2-type cells, which were found to be induced by low concentrations of IL-35 compatible with those produced by human trophoblasts, are exclusively present in the decidua of a successful pregnancy and at the embryo implantation site, suggesting their stringent dependence on trophoblast cells. Thus, the proximity of Th cells to IL-35-producing trophoblasts could be the determining factor for the differentiation of IL-35+, IL-10+, IL-4+ Th2-type cells that are crucial for human pregnancy success. |
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| id | doaj.art-28134b25fd8247b0b8455ee8ee0e1f1d |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:04Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-28134b25fd8247b0b8455ee8ee0e1f1d2023-11-23T08:24:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239492610.3390/ijms23094926At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy SuccessLetizia Lombardelli0Federica Logiodice1Ornela Kullolli2Herman Haller3Chiara Agostinis4Roberta Bulla5Daniel Rukavina6Marie-Pierre Piccinni7Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Gynecology and Obstetrics, Medical Faculty, University of Rijeka, 51000 Rijeka, CroatiaInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, 51000 Rijeka, CroatiaDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyWe investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human trophoblast cells produced IL-35 but not IL-4 or IL-10. RhIL-35, at concentrations produced by human trophoblasts, polarized T cells towards IL-35+, IL-10+, IL-4+ Th2-type cells and to Foxp3+ EBI3+ p35+ T reg cells producing IL-35 but not IL-10 and IL-4. Moreover, rhIL-35 at low concentrations did not suppress the proliferation of Th cells but stimulated IL-4 and IL-10 production by established Th clones. In particular, Th1-type clones acquired the capacity to produce IL-4. In addition, purified human trophoblast cell supernatants containing IL-35 upregulated IL-4 and IL-10 production by Th clones. Finally, IL-35+, IL-10+, IL-4+ Th2-type cells, which were found to be induced by low concentrations of IL-35 compatible with those produced by human trophoblasts, are exclusively present in the decidua of a successful pregnancy and at the embryo implantation site, suggesting their stringent dependence on trophoblast cells. Thus, the proximity of Th cells to IL-35-producing trophoblasts could be the determining factor for the differentiation of IL-35+, IL-10+, IL-4+ Th2-type cells that are crucial for human pregnancy success.https://www.mdpi.com/1422-0067/23/9/4926IL-35IL-4IL-10pregnancyTh2 cellsTreg cells |
| spellingShingle | Letizia Lombardelli Federica Logiodice Ornela Kullolli Herman Haller Chiara Agostinis Roberta Bulla Daniel Rukavina Marie-Pierre Piccinni At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success International Journal of Molecular Sciences IL-35 IL-4 IL-10 pregnancy Th2 cells Treg cells |
| title | At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success |
| title_full | At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success |
| title_fullStr | At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success |
| title_full_unstemmed | At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success |
| title_short | At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success |
| title_sort | at embryo implantation site il 35 secreted by trophoblast polarizing t cells towards il 35 il 10 il 4 th2 type cells could favour fetal allograft tolerance and pregnancy success |
| topic | IL-35 IL-4 IL-10 pregnancy Th2 cells Treg cells |
| url | https://www.mdpi.com/1422-0067/23/9/4926 |
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