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. 2020 Dec;21(12):1517-1527.
doi: 10.1038/s41590-020-00811-2. Epub 2020 Nov 9.

CRELD1 modulates homeostasis of the immune system in mice and humans

Lorenzo Bonaguro  1   2 , Maren Köhne  1   3 , Lisa Schmidleithner  1   3 , Jonas Schulte-Schrepping  1 , Stefanie Warnat-Herresthal  1 , Arik Horne  1 , Paul Kern  2   4 , Patrick Günther  1 , Rob Ter Horst  5 , Martin Jaeger  5 , Souad Rahmouni  6 , Michel Georges  6 , Christine S Falk  7 , Yang Li  5   8 , Elvira Mass  4 , Marc Beyer  1   3 , Leo A B Joosten  5 , Mihai G Netea  5   9 , Thomas Ulas  1   10 , Joachim L Schultze  1   10 , Anna C Aschenbrenner  11   12
Affiliations

CRELD1 modulates homeostasis of the immune system in mice and humans

Lorenzo Bonaguro et al. Nat Immunol. 2020 Dec.

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.

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Comment in

  • CRELD1 controls T cell homeostasis.
    Gounari F. Gounari F. Nat Immunol. 2020 Dec;21(12):1480-1482. doi: 10.1038/s41590-020-00820-1. Nat Immunol. 2020. PMID: 33169012 Free PMC article. No abstract available.

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