Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia

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Wedenoja , S , Yoshihara , M , Teder , H , Sariola , H , Gissler , M , Katayama , S , Wedenoja , J , Häkkinen , I M K , Ezer , S , Linder , N , Lundin , J , Skoog , T , Sahlin , E , Iwarsson , E , Pettersson , K , Kajantie , E , Mokkonen , M , Heinonen , S , Laivuori , H , Krjutskov , K & Kere , J 2020 , ' Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia ' , EBioMedicine , vol. 59 , 102872 . https://doi.org/10.1016/j.ebiom.2020.102872

Title: Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
Author: Wedenoja, Satu; Yoshihara, Masahito; Teder, Hindrek; Sariola, Hannu; Gissler, Mika; Katayama, Shintaro; Wedenoja, Juho; Häkkinen, Inka M. K.; Ezer, Sini; Linder, Nina; Lundin, Johan; Skoog, Tiina; Sahlin, Ellika; Iwarsson, Erik; Pettersson, Karin; Kajantie, Eero; Mokkonen, Mikael; Heinonen, Seppo; Laivuori, Hannele; Krjutskov, Kaarel; Kere, Juha
Contributor organization: HUS Gynecology and Obstetrics
University of Helsinki
Helsinki University Hospital Area
STEMM - Stem Cells and Metabolism Research Program
Research Programs Unit
Helsinki One Health (HOH)
HUSLAB
Hannu Sariola / Principal Investigator
Department of Biochemistry and Developmental Biology
Clinicum
Department of Ophthalmology and Otorhinolaryngology
Faculty of Medicine
Medicum
Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
Johan Edvard Lundin / Principal Investigator
HUS Children and Adolescents
Lastentautien yksikkö
Children's Hospital
Department of Obstetrics and Gynecology
Genomics of Neurological and Neuropsychiatric Disorders
Pregnancy and Genes
Department of Medical and Clinical Genetics
Juha Kere / Principal Investigator
Date: 2020-09
Language: eng
Number of pages: 13
Belongs to series: EBioMedicine
ISSN: 2352-3964
DOI: https://doi.org/10.1016/j.ebiom.2020.102872
URI: http://hdl.handle.net/10138/320560
Abstract: Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses. Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFN alpha) protein expression by immunohistochemistry. Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas. Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials. (C) 2020 The Authors. Published by Elsevier B.V.
Subject: 3' UNTRANSLATED REGION
BALANCING SELECTION
Balancing selection
EXTRAVILLOUS TROPHOBLASTS
GENE-EXPRESSION
HLA-G
I INTERFERONS
Interferon alpha
MATERNAL CIRCULATION
PREGNANCY
Preeclampsia
SELECTIVE ADVANTAGE
SEX-RATIO
SINGLE-CELL TRANSCRIPTOME
Sex ratio
Stillbirth
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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