Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-08-19 DOI:10.1016/j.xcrm.2025.102285

Lev Petrov, Sophia Brumhard, Sebastian Wisniewski, Philipp Georg, David Hillus, Anna Hiller, Rosario Astaburuaga-García, Nils Blüthgen, Emanuel Wyler, Katrin Vogt, Hannah-Philine Dey, Saskia von Stillfried, Christina Iwert, Roman D Bülow, Bruno Märkl, Lukas Maas, Christine Langner, Tim Meyer, Jennifer Loske, Roland Eils, Irina Lehmann, Benjamin Ondruschka, Markus Ralser, Jakob Trimpert, Peter Boor, Sammy Bedoui, Christian Meisel, Marcus A Mall, Victor M Corman, Leif Erik Sander, Jobst Röhmel, Birgit Sawitzki

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引用次数: 0

Abstract

Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of 164 samples from SARS-CoV-2-infected persons aged 1 to 84 years reveals a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4⁺ T cells, and B cells with increasing age. Diversion of IFN signaling is associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4⁺ T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69^high GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.

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重新连接的I型IFN信号与COVID-19的年龄依赖性差异有关。

高龄是导致COVID-19严重疾病或死亡的最重要风险因素，但对其分子和细胞基础缺乏透彻的机制理解。对164例年龄在1岁至84岁的sars - cov -2感染者的多组学分析显示，随着年龄的增长，单核细胞、CD4+ T细胞和B细胞中的I型干扰素（IFN）信号通路从信号换能器和转录激活器1 （STAT1）逐渐转变为STAT3激活。IFN信号的转移与炎症标志物的表达增加、炎症细胞因子的释放增强以及感染诱导的CD4+ T细胞的延迟收缩有关。在衰老过程中，从ifn应答性生发中心B （GCB）细胞向cd69高的GCB和非典型B细胞的转变与儿童免疫球蛋白（Ig）A的产生相关，而补体固定IgG在成人中占主导地位。我们的数据为衰老过程中感染和相关病理的炎症倾向反应提供了机制基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.