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

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机构： [1]Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [3]Frontier Medical Center, Xin Chuan Road, Zhong He Street, 610212, Chengdu, Sichuan, China. [4]Department of Orthodontics, State Key laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. [5]Department of Anesthesiology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. [6]Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [7]Department of Intensive Care Unit of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

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关键词： Sepsis Adaptive Immunosuppression Amyloid-β (Aβ) CD47 SIRP

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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.© 2025. The Author(s).

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出版当年[2025]版：

大类 | 1 区

生物学

小类 | 2 区生化与分子生物学 2 区细胞生物学

最新[2025]版：

大类 | 1 区

生物学

小类 | 2 区生化与分子生物学 2 区细胞生物学

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第一作者机构： [1]Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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