CRELD1 modulates homeostasis of the immune system in mice and humans

[en] CRELD1 is a pivotal factor for heart development, the function of which is unknown in adult life. We here provide evidence that CRELD1 is an important gatekeeper of immune system homeostasis. Exploiting expression variance in large human cohorts contrasting individuals with the lowest and highest CRELD1 expression levels revealed strong phenotypic, functional and transcriptional differences, including reduced CD4+ T cell numbers. These findings were validated in T cell-specific Creld1-deficient mice. Loss of Creld1 was associated with simultaneous overactivation and increased apoptosis, resulting in a net loss of T cells with age. Creld1 was transcriptionally and functionally linked to Wnt signaling. Collectively, gene expression variance in large human cohorts combined with murine genetic models, transcriptomics and functional testing defines CRELD1 as an important modulator of immune homeostasis.

Disciplines :

Immunology & infectious disease

Author, co-author :

Bonaguro, Lorenzo

Köhne, Maren

Schmidleithner, Jonas

Warnat-Herresthal, Stefanie

Horne, Arik

Kern, Paul

Günther, Patrick

Ter Horst, Rob

Jaeger, Martin

Rahmouni, Souad ; Université de Liège - ULiège > Medical Genomics-Unit of Animal Genomics

More authors (10 more)

Language :

English

Title :

CRELD1 modulates homeostasis of the immune system in mice and humans

Publication date :

21 December 2020

Journal title :

Nature Immunology

ISSN :

1529-2908

eISSN :

1529-2916

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Pages :

1517-1527

Peer reviewed :

Peer Reviewed verified by ORBi

European Projects :

H2020 - 733100 - SYSCID - A Systems medicine approach to chronic inflammatory disease

Funders :

CE - Commission Européenne [BE]

Available on ORBi :

since 20 January 2021

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