An integrative genomics approach identifies KDM4 as a modulator of trained immunity.
KDM4
QTL mapping
immunogenomics
innate immune memory
trained immunity
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
29
09
2021
received:
29
09
2021
accepted:
19
11
2021
pubmed:
26
11
2021
medline:
6
5
2022
entrez:
25
11
2021
Statut:
ppublish
Résumé
Innate immune cells are able to build memory characteristics via a process termed "trained immunity." Host factors that influence the magnitude of the individual trained immunity response remain largely unknown. Using an integrative genomics approach, our study aimed to prioritize and understand the role of specific genes in trained immunity responses. In vitro-induced trained immunity responses were assessed in two independent population-based cohorts of healthy individuals, the 300 Bacillus Calmette-Guérin (300BCG; n = 267) and 200 Functional Genomics (200FG; n = 110) cohorts from the Human Functional Genomics Project. Genetic loci that influence cytokine responses upon trained immunity were identified by conducting a meta-analysis of QTLs identified in the 300BCG and 200FG cohorts. From the identified QTL loci, we functionally validated the role of PI3K-Akt signaling pathway and two genes that belong to the family of Siglec receptors (Siglec-5 and Siglec-14). Furthermore, we identified the H3K9 histone demethylases of the KDM4 family as major regulators of trained immunity responses. These data pinpoint an important role of metabolic and epigenetic processes in the regulation of trained immunity responses, and these findings may open new avenues for vaccine design and therapeutic interventions.
Identifiants
pubmed: 34821391
doi: 10.1002/eji.202149577
pmc: PMC9299854
doi:
Substances chimiques
BCG Vaccine
0
Sialic Acid Binding Immunoglobulin-like Lectins
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
431-446Informations de copyright
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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