Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 07 2022
29 07 2022
Historique:
received:
28
09
2021
accepted:
18
07
2022
entrez:
29
7
2022
pubmed:
30
7
2022
medline:
3
8
2022
Statut:
epublish
Résumé
Fetal growth restriction (FGR) affects 5-10% of pregnancies, and can have serious consequences for both mother and child. Prevention and treatment are limited because FGR pathogenesis is poorly understood. Genetic studies implicate KIR and HLA genes in FGR, however, linkage disequilibrium, genetic influence from both parents, and challenges with investigating human pregnancies make the risk alleles and their functional effects difficult to map. Here, we demonstrate that the interaction between the maternal KIR2DL1, expressed on uterine natural killer (NK) cells, and the paternally inherited HLA-C*0501, expressed on fetal trophoblast cells, leads to FGR in a humanized mouse model. We show that the KIR2DL1 and C*0501 interaction leads to pathogenic uterine arterial remodeling and modulation of uterine NK cell function. This initial effect cascades to altered transcriptional expression and intercellular communication at the maternal-fetal interface. These findings provide mechanistic insight into specific FGR risk alleles, and provide avenues of prevention and treatment.
Identifiants
pubmed: 35906236
doi: 10.1038/s41467-022-32171-w
pii: 10.1038/s41467-022-32171-w
pmc: PMC9338297
doi:
Substances chimiques
HLA-C Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4398Subventions
Organisme : Wellcome Trust
ID : 100956/Z/13/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12025
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/3
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : RC2 DK116691
Pays : United States
Organisme : Wellcome Trust
ID : 100308/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0902418
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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