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Publication : CRELD1 modulates homeostasis of the immune system in mice and humans.

First Author  Bonaguro L Year  2020
Journal  Nat Immunol Volume  21
Issue  12 Pages  1517-1527
PubMed ID  33169013 Mgi Jnum  J:305788
Mgi Id  MGI:6706623 Doi  10.1038/s41590-020-00811-2
Citation  Bonaguro L, et al. (2020) CRELD1 modulates homeostasis of the immune system in mice and humans. Nat Immunol 21(12):1517-1527
abstractText  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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