Immunologic Research

, Volume 67, Issue 1, pp 77–83 | Cite as

FcRγ deficiency improves survival in experimental sepsis by down-regulating TLR4 signaling pathway

  • Zhi-Min Wei
  • Zhuo Wang
  • Xiao-Jian Wan
  • Xian-Jing Li
  • Yi-Xing Li
  • Yang Bai
  • Xue Yang
  • Yong YangEmail author
  • Shun-Chang JiaoEmail author
  • Zhe-Feng LiuEmail author
Original Article


Fc receptor common γ signaling chain (FcRγ), a common subunit shared by Fc receptors (FcγRI, III, IV, FcαRI, and FcεRI), is an important immune regulator both in innate and adaptive immunity. Previous studies have shown that FcRγ was a potential target of inflammatory diseases, whereas the role of FcRγ in sepsis has been poorly understood. In this study, we found that deficiency of FcRγ resulted in increased survival in lipopolysaccharide (LPS)/D-galactosamine and E. coli-induced sepsis in mice. This protective effect was characterized by decreased TNF-α, IL-6, and IL-10. Further experiments in bone marrow-derived macrophages (BMDMs) in vitro also showed that FcRγ deficiency resulted in decreased production of TNF-α, IL-6, and IL-10 upon LPS stimulation. The mechanism study showed that FcRγ was physiologically associated with toll-like receptor 4 (TLR4), and tyrosine phosphorylation of FcRγ mediated TLR4 signaling pathway, followed by increased ERK phosphorylation upon LPS stimulation. Our results suggest that FcRγ might be a potential therapeutic target of sepsis.





Fc receptor common γ signaling chain


Toll-like receptor 4




Pathogen-associated molecule patterns






Bone marrow-derived macrophages


Immunoreceptor tyrosine-based activation motif


Spleen tyrosine kinase


Phospholipase C-γ


Tumor necrosis factor α


Interleukin 6


Interleukin 10


Phosphorylation of tyrosine




Funding information

This work was supported in part by the National Science Foundation of China (Nos. 91529304, 81473230, and 81673468) and the Natural Science Foundation of Jiangsu Province (No. BK20170732).

Compliance with ethical standards

All animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Center for New Drug Evaluation and Research, China Pharmaceutical University, Nanjing, China.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OncologyGeneral Hospital of Chinese PLABeijingChina
  2. 2.State Key Laboratory of Natural Medicines, Center for New Drug Safety Evaluation and ResearchChina Pharmaceutical UniversityNanjingChina
  3. 3.School of PharmacyNanjing University of Chinese MedicineNanjingChina
  4. 4.Department of Anesthesiology and Intensive Care Medicine, Changhai HospitalSecond Military Medical UniversityShanghaiChina

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