Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis

Peng-Yue Zhao; Ren-Qi Yao; Li-Yu Zheng; Yao Wu; Yu-Xuan Li; Ning Dong; Jing-Yan Li; Xiao-Hui Du; Yong-Ming Yao

doi:10.1093/burnst/tkac055

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Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis

更新时间：2023-05-16

- Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis
- Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis
- Burns & Trauma 2023年11卷第1期
- 作者机构：
  
  1. Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital
  2. Department of General Surgery, First Medical Center of the Chinese PLA General Hospital
  3. Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University
  4. Department of Emergency, The Second Hospital of Hebei Medical University
- 作者简介：
- 基金信息：
  
  This work was supported by grants from the National Natural Sciences Foundation of China (Nos. 81 730 057, 82 130 062, 81 801 935), Key Project of Military Medical Innovation Program of Chinese PLA (Nos. 18CXZ025, 18CXZ026) and Provincial Key Project of Medical Science Research of Hebei (20 210 013).
- DOI：10.1093/burnst/tkac055
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-2-28，
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Peng-Yue Zhao, Ren-Qi Yao, Li-Yu Zheng, 等. Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis[J]. Burns & Trauma, 2023,11(1).

Peng-Yue Zhao, Ren-Qi Yao, Li-Yu Zheng, Yao Wu, Yu-Xuan Li, Ning Dong, Jing-Yan Li, Xiao-Hui Du, Yong-Ming Yao, Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis, Burns & Trauma, Volume 11, 2023, tkac055, https://doi.org/10.1093/burnst/tkac055
Peng-Yue Zhao, Ren-Qi Yao, Li-Yu Zheng, 等. Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis[J]. Burns & Trauma, 2023,11(1). DOI： 10.1093/burnst/tkac055.

Peng-Yue Zhao, Ren-Qi Yao, Li-Yu Zheng, Yao Wu, Yu-Xuan Li, Ning Dong, Jing-Yan Li, Xiao-Hui Du, Yong-Ming Yao, Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis, Burns & Trauma, Volume 11, 2023, tkac055, https://doi.org/10.1093/burnst/tkac055 DOI：

摘要

Abstract

BackgroundRibophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular homeostasis. Whether ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy (ERphagy) and mitophagy remains unclear. This study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte apoptosis.MethodsThe activity and regulation of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting

laser confocal microscopy and transmission electron microscopy. Then

we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic challenge.ResultsBoth cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy

which peaked at 24 h. When NUFIP1 was knocked down

T-lymphocyte apoptosis was noticeably increased. Conversely

the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte apoptosis. Consistently

the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type mice. In addition

the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway

and PERK–ATF4–CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of sepsis.ConclusionsNUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK–ATF4–CHOP pathway in the context of sepsis. Thus

targeting NUFIP1-mediated ribophagy might be of importance in reversing the immunosuppression associated with septic complications.

关键词

Keywords

NUFIP1RibophagySepsisApoptosisImmunosuppressionAutophagyMitophagyLymphocyteLipopolysaccharide

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