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Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua

The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cel...

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Autores principales: Silasi, Michelle, You, Yuan, Simpson, Samantha, Kaislasuo, Janina, Pal, Lubna, Guller, Seth, Peng, Gang, Ramhorst, Rosanna, Grasso, Esteban, Etemad, Shervin, Durosier, Sandy, Aldo, Paulomi, Mor, Gil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113245/
https://www.ncbi.nlm.nih.gov/pubmed/32238853
http://dx.doi.org/10.1038/s41598-020-62593-9
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author Silasi, Michelle
You, Yuan
Simpson, Samantha
Kaislasuo, Janina
Pal, Lubna
Guller, Seth
Peng, Gang
Ramhorst, Rosanna
Grasso, Esteban
Etemad, Shervin
Durosier, Sandy
Aldo, Paulomi
Mor, Gil
author_facet Silasi, Michelle
You, Yuan
Simpson, Samantha
Kaislasuo, Janina
Pal, Lubna
Guller, Seth
Peng, Gang
Ramhorst, Rosanna
Grasso, Esteban
Etemad, Shervin
Durosier, Sandy
Aldo, Paulomi
Mor, Gil
author_sort Silasi, Michelle
collection PubMed
description The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy.
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spelling pubmed-71132452020-04-06 Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua Silasi, Michelle You, Yuan Simpson, Samantha Kaislasuo, Janina Pal, Lubna Guller, Seth Peng, Gang Ramhorst, Rosanna Grasso, Esteban Etemad, Shervin Durosier, Sandy Aldo, Paulomi Mor, Gil Sci Rep Article The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy. Nature Publishing Group UK 2020-04-01 /pmc/articles/PMC7113245/ /pubmed/32238853 http://dx.doi.org/10.1038/s41598-020-62593-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Silasi, Michelle
You, Yuan
Simpson, Samantha
Kaislasuo, Janina
Pal, Lubna
Guller, Seth
Peng, Gang
Ramhorst, Rosanna
Grasso, Esteban
Etemad, Shervin
Durosier, Sandy
Aldo, Paulomi
Mor, Gil
Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title_full Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title_fullStr Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title_full_unstemmed Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title_short Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
title_sort human chorionic gonadotropin modulates cxcl10 expression through histone methylation in human decidua
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113245/
https://www.ncbi.nlm.nih.gov/pubmed/32238853
http://dx.doi.org/10.1038/s41598-020-62593-9
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