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14.12.2018 | Original Article

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

verfasst von: Zhi-Min Wei, Zhuo Wang, Xiao-Jian Wan, Xian-Jing Li, Yi-Xing Li, Yang Bai, Xue Yang, Yong Yang, Shun-Chang Jiao, Zhe-Feng Liu

Erschienen in: Immunologic Research | Ausgabe 1/2019

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Abstract

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.

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Titel: FcRγ deficiency improves survival in experimental sepsis by down-regulating TLR4 signaling pathway
verfasst von: Zhi-Min Wei
Zhuo Wang
Xiao-Jian Wan
Xian-Jing Li
Yi-Xing Li
Yang Bai
Xue Yang
Yong Yang
Shun-Chang Jiao
Zhe-Feng Liu
Publikationsdatum: 14.12.2018
Verlag: Springer US
Erschienen in: Immunologic Research / Ausgabe 1/2019
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-018-9039-y

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

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