| Literature DB >> 33169013 |
Lorenzo Bonaguro1,2, Maren Köhne1,3, Lisa Schmidleithner1,3, Jonas Schulte-Schrepping1, Stefanie Warnat-Herresthal1, Arik Horne1, Paul Kern2,4, Patrick Günther1, Rob Ter Horst5, Martin Jaeger5, Souad Rahmouni6, Michel Georges6, Christine S Falk7, Yang Li5,8, Elvira Mass4, Marc Beyer1,3, Leo A B Joosten5, Mihai G Netea5,9, Thomas Ulas1,10, Joachim L Schultze1,10, Anna C Aschenbrenner11,12.
Abstract
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.Entities:
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Year: 2020 PMID： 33169013 DOI： 10.1038/s41590-020-00811-2
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606