Preprint / Version 2

STAT1-driven FcRn suppression in macrophages limits antibody protection during bacterial sepsis

This article is a preprint and has not been certified by peer review.

Authors

    Xinyu Wei,  
    Xinyu Wei
    Xiaoxia Su,  
    Xiaoxia Su
    Qianyu Duan,  
    Qianyu Duan
    Miao Pei,  
    Miao Pei
    Qun Huang,  
    Qun Huang
    Xuan Lai,  
    Xuan Lai
    Jiani Zhang,  
    Jiani Zhang
    Danzhi Wu,  
    Danzhi Wu
    Beibei Chen,  
    Beibei Chen
    Yu Deng,  
    Yu Deng
    Ying Huang,  
    Ying Huang
    Jinzhou Ye,  
    Jinzhou Ye
    Teng Zhang,  
    Teng Zhang
    Hua Zhou,  
    Hua Zhou
    • the Second Affiliated Hospital Zhejiang University
    Xiaoting Hua,  
    Xiaoting Hua
    • Sir Run Run Shaw Hospital image/svg+xml
    • Zhejiang Provincial Engineering Research Center of Innovative Instruments for Precise Pathogen Detection
    Xin Ding,  
    Xin Ding
    • Shenzhen Campus of Sun Yat-sen University
    Mao Li,  
    Mao Li
    Xianjie Liu,  
    Xianjie Liu
    • Shenzhen International Institute for Biomedical Research
    Wenjun Chen,  
    Wenjun Chen
    Xinhai Chen
    Xinhai Chen
    • Shenzhen Bay Laboratory image/svg+xml
    • Shenzhen Medical Academy of Research and Translation image/svg+xml
    • Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation
Categories
Immunology & Microbiology
Keywords
IgG; Bacterial sepsis; Macrophage; FcRn; STAT1

Abstract

Sepsis is frequently accompanied by reduced circulating IgG levels, but the mechanism and therapeutic implications remain unclear. Here, we show that bacterial sepsis accelerates clearance of both endogenous and therapeutic IgG independently of antigen specificity. Lipopolysaccharide and peptidoglycan activate STAT1 in hepatic and splenic macrophages, leading to selective downregulation of the neonatal Fc receptor (FcRn), impaired IgG recycling, and enhanced intracellular degradation. Macrophage-specific deletion of Fcgrt abolishes sepsis-induced IgG loss, whereas genetic or pharmacologic inhibition of STAT1 restores FcRn expression, preserves circulating IgG, and enhances the protective efficacy of intravenous immunoglobulin and pathogen-specific monoclonal antibodies. In human sepsis, reduced FcRn expression in monocytes correlates with poor outcome, and bacterial or PAMP stimulation suppresses FcRn and IgG transcytosis in primary macrophages in a STAT1-dependent manner. These findings identify STAT1-driven suppression of macrophage FcRn as a conserved mechanism limiting antibody protection during bacterial sepsis.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.02.12.000130

Submission ID:

130

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Posted

2026-03-04

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How to Cite

Wei, X., Su, X., Duan, Q., Pei, M., Huang, Q., Lai, X., Zhang, J., Wu, D., Chen, B., Deng, Y., Huang, Y., Ye, J., Zhang, T., Zhou, H., Hua, X., Ding, X., Li, M., Liu, X., Chen, W., & Chen, X. (2026). STAT1-driven FcRn suppression in macrophages limits antibody protection during bacterial sepsis. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.02.12.000130

Declaration of Competing Interests

The authors declare no competing interests to disclose.

Copyright

The copyright holder for this preprint is the author/funder.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.