德国波恩大学Anna C. Aschenbrenner研究小组在研究中取得进展。他们研究发现在人和小鼠中CRELD1调节免疫系统的体内稳态。2020年11月9日，国际学术期刊《自然-免疫学》发表了这一成果。

研究人员发现CRELD1是免疫系统稳态的重要守护因子。在包含大量具有最低和最高CRELD1表达个体的对比研究中，研究发现CRELD1表达差异具有显著的表型、功能和转录差异，包括CD4⁺ T细胞数量的减少。

这些发现在T细胞特异性Creld1缺陷小鼠中得到了验证。Creld1缺失伴随着过度激活和凋亡增加，这导致T细胞数量随着年龄的增长而降低。Creld1在转录和功能上与Wnt信号相关。

总的来说，包含大量个体基因表达差异的研究与小鼠遗传模型、转录组学和功能测试相结合，确定了CRELD1在免疫稳态中的重要调节作用。

研究人员表示，CRELD1是心脏发育的关键调节因子，其在成年人中的功能是未知的。

附：英文原文

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

Author: Lorenzo Bonaguro, Maren Khne, Lisa Schmidleithner, Jonas Schulte-Schrepping, Stefanie Warnat-Herresthal, Arik Horne, Paul Kern, Patrick Gnther, Rob ter Horst, Martin Jaeger, Souad Rahmouni, Michel Georges, Christine S. Falk, Yang Li, Elvira Mass, Marc Beyer, Leo A. B. Joosten, Mihai G. Netea, Thomas Ulas, Joachim L. Schultze, Anna C. Aschenbrenner

Issue&Volume: 2020-11-09

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. Within a human cohort, wide variation can occur with constitutively expressed proteins. Aschenbrenner and colleagues found that individuals with lower CRELD1 expression have decreased frequencies of naive CD4+ T cells. Mice with conditional Creld1 deficiency also exhibit a phenotype associated with immunological aging.

DOI: 10.1038/s41590-020-00811-2

Source: https://www.nature.com/articles/s41590-020-00811-2