PGRMC2 and HLA-G regulate immune homeostasis in a microphysiological model of human maternal-fetal membrane interface.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
13
02
2024
accepted:
15
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
Chorion trophoblasts (CTCs) and immune cell-enriched decidua (DECs) comprise the maternal-fetal membrane interface called the chorio-decidual interface (CDi) which constantly gets exposed to maternal stressors without leading to labor activation. This study explored how CTCs act as a barrier at CDi. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating immune homeostasis were also investigated. The CDi was recreated in a two-chamber microfluidic device (CDi-on-chip) with an outer chamber of primary DECs and immune cell line-derived innate immune cells and an inner chamber of wild-type or PGRMC2 or HLA-G knockout immortalized CTCs. To mimic maternal insults, DECs were treated with lipopolysaccharide, poly(I:C), or oxidative stress inducer cigarette smoke extract. Expression levels of inflammation and immunity genes via targeted RNA sequencing, production of soluble mediators, and immune cell migration into CTCs were determined. In CDi-on-chip, decidua and immune cells became inflammatory in response to insults while CTCs were refractory, highlighting their barrier function. HLA-G and PGRMC2 are found to be vital to immune homeostasis at the CDi, with PGRMC2 serving as an upstream regulator of inflammation, HLA-G expression, and mesenchymal-epithelial transition, and HLA-G serving as a frontline immunomodulatory molecule, thus preventing fetal membrane compromise.
Identifiants
pubmed: 39179795
doi: 10.1038/s42003-024-06740-2
pii: 10.1038/s42003-024-06740-2
doi:
Substances chimiques
HLA-G Antigens
0
Receptors, Progesterone
0
Membrane Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1041Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)
ID : UH3TR003283-03
Organisme : U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)
ID : UH2TR004117-01
Informations de copyright
© 2024. The Author(s).
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