CD47-amyloid-β-CD74 signaling triggers adaptive immunosuppression in sepsis.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI:10.1038/s44319-025-00442-4

Zhongxue Feng, Lijun Wang, Yang Li, Yonggang Wei, Yueyue Zhou, Siying Wang, Xiaoqi Zhang, Chunling Jiang, Xuelian Liao, Yan Kang, Fei Xiao, Wei Zhang

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Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. However, how this dysregulation occurs remains to be elucidated. In this study, we use single-cell RNA sequencing (scRNA-seq) and conventional RNA-seq to analyze the immune landscape of sepsis and observe that adaptive immunity is acutely and strongly suppressed. This systemic immunosuppression occurs not only in the peripheral blood but also in all other immune compartments, including the spleen, lymph nodes, and bone marrow. Clinical data show that these adaptive immunity-related genes may have the potential to be used to distinguish patients with sepsis from those with common infections. CD47 is found to play a pivotal role in this immunosuppression by inducing the production of amyloid-β (Aβ), which interacts with CD74 on B cells, leading to B-cell suppression and subsequent adaptive immunosuppression. Blocking CD47-Aβ signaling significantly reduces organ injury and improves the survival rate of septic mice by restoring phagocytic cell functions and alleviating B-cell suppression and adaptive immunosuppression.

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cd47 -淀粉样蛋白-β-CD74信号在脓毒症中引发适应性免疫抑制。

脓毒症被定义为由宿主对感染反应失调引起的危及生命的器官功能障碍。然而，这种失调是如何发生的仍有待阐明。在本研究中，我们使用单细胞RNA测序（scRNA-seq）和常规RNA-seq分析脓毒症的免疫景观，观察到适应性免疫受到急性和强烈的抑制。这种全身性免疫抑制不仅发生在外周血，也发生在所有其他免疫区，包括脾脏、淋巴结和骨髓。临床数据显示，这些适应性免疫相关基因可能有潜力用于区分脓毒症患者和普通感染患者。研究发现，CD47通过诱导淀粉样蛋白-β (a β)的产生在这种免疫抑制中发挥关键作用，淀粉样蛋白-β与B细胞上的CD74相互作用，导致B细胞抑制和随后的适应性免疫抑制。阻断cd47 - a - β信号可通过恢复吞噬细胞功能，减轻b细胞抑制和适应性免疫抑制，显著减轻脏器损伤，提高脓毒症小鼠存活率。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.