Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Developmental Genetics & Molecular Physiology, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Nat Immunol. 2020 Dec;21(12):1517-1527. doi: 10.1038/s41590-020-00811-2. Epub 2020 Nov 9.
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.
CRELD1 是心脏发育的关键因素，但其在成人生活中的功能尚不清楚。我们在这里提供的证据表明，CRELD1 是免疫系统稳态的重要守门员。利用在对比个体 CRELD1 表达水平最低和最高的大型人群中的表达差异，揭示了明显的表型、功能和转录差异，包括 CD4 T 细胞数量减少。在 T 细胞特异性 Creld1 缺陷小鼠中验证了这些发现。Creld1 的缺失与同时的过度激活和增加的细胞凋亡有关，导致随着年龄的增长 T 细胞数量净损失。Creld1 在转录和功能上与 Wnt 信号通路相关。总的来说，大型人群中的基因表达差异与小鼠遗传模型、转录组学和功能测试相结合，将 CRELD1 定义为免疫稳态的重要调节剂。
