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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
01 04 2020
Historique:
received: 24 09 2019
accepted: 12 03 2020
entrez: 3 4 2020
pubmed: 3 4 2020
medline: 15 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32238853
doi: 10.1038/s41598-020-62593-9
pii: 10.1038/s41598-020-62593-9
pmc: PMC7113245
doi:

Substances chimiques

CXCL10 protein, human 0
Chemokine CXCL10 0
Chorionic Gonadotropin 0
Histones 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5785

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI145829
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD047018
Pays : United States

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Kaislasuo, J. et al. IL-10 to TNFalpha ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses. Am. J. Reprod. Immunol., e13195 (2019).

Auteurs

Michelle Silasi (M)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Yuan You (Y)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.
C.S. Mott Center for Human Growth and Development, Department of Obstetrics, Gynecology, Wayne State University, Detroit, MI, USA.

Samantha Simpson (S)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Janina Kaislasuo (J)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.
Department of Obstetrics and Gynecology, University of Helsinki and the Helsinki University Hospital, Helsinki, Finland.

Lubna Pal (L)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Seth Guller (S)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Gang Peng (G)

Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA.

Rosanna Ramhorst (R)

Laboratory of Immunopharmacology, University of Buenos Aires School of Sciences, IQUIBICEN-CONICET (National Research Council), Buenos Aires, Argentina.

Esteban Grasso (E)

Laboratory of Immunopharmacology, University of Buenos Aires School of Sciences, IQUIBICEN-CONICET (National Research Council), Buenos Aires, Argentina.

Shervin Etemad (S)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Sandy Durosier (S)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Paulomi Aldo (P)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA.

Gil Mor (G)

Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, USA. gmor@med.wayne.edu.
C.S. Mott Center for Human Growth and Development, Department of Obstetrics, Gynecology, Wayne State University, Detroit, MI, USA. gmor@med.wayne.edu.

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