Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 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：
DOI：10.1093/burnst/tkac055
CLC：Published：2023，
Published Online：28 February 2023，
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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, 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
references
1.Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.
2.Angus DC, Bindman AB. Achieving diagnostic excellence for sepsis. JAMA. 2022;327:117–8.
3.Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study. Lancet. 2020;395:200–11.
4.Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394:1949–64.
5.Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–74.
6.Long J, Yang C, Zheng Y, Loughran P, Guang F, Li Y, et al. Notch signaling protects CD4 T cells from STING-mediated apoptosis during acute systemic inflammation. Sci Adv. 2020;6:eabc5447.
7.Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14:121–37.
8.Huang S, Liu D, Sun J, Zhang H, Zhang J, Wang Q, et al. Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-κB signaling pathway in CD4 T cells. Mol Ther. 2022;30:1227–38.
9.Huang L, Zhang X, Fan J, Liu X, Luo S, Cao D, et al. EGFR promotes the apoptosis of CD4+ T lymphocytes through TBK1/Glut1 induced Warburg effect in sepsis. J Adv Res. 2022;S2090-1232:00106-0. https://doi.org/10.1016/j.jare.2022.04.010.
10.Ren C, Li XH, Wang SB, Wang LX, Dong N, Wu Y, et al. Activation of central alpha 7 nicotinic acetylcholine receptor reverses suppressed immune function of T lymphocytes and protects against sepsis lethality. Int J Biol Sci. 2018;14:748–59.
11.Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med. 1997;25:1298–307.
12.Hotchkiss RS, Swanson PE, Knudson CM, Chang KC, Cobb JP, Osborne DF, et al. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol. 1999;162:4148–56.
13.Nakanishi T, Nishi Y, Sato EF, Ishii M, Hamada T, Inoue M. Thermal injury induces thymocyte apoptosis in the rat. J Trauma. 1998;44:143–8.
14.Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Jr, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166:6952–63.
15.Yao YM, Zhang H. Rehabilitation strategy for the improvement of long-term outcomes of patients after sepsis. Chin J Burns Wounds. 2022;38:201–6.
16.Zhao PY, Yao RQ, Zhang ZC, Zhu SY, Li YX, Ren C, et al. Eukaryotic ribosome quality control system: a potential therapeutic target for human diseases. Int J Biol Sci. 2022;18:2497–514.
17.Kraft C, Deplazes A, Sohrmann M, Peter M. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol. 2008;10:602–10.
18.Wyant GA, Abu-Remaileh M, Frenkel EM, Laqtom NN, Dharamdasani V, Lewis CA, et al. NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science. 2018;360:751–8.
19.Xia H, Green DR, Zou W. Autophagy in tumour immunity and therapy. Nat Rev Cancer. 2021;21:281–97.
20.Yao RQ, Ren C, Xia ZF, Yao YM. Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles. Autophagy. 2021;17:385–401.
21.Zhang Q, Kuang H, Chen C, Yan J, Do-Umehara HC, Liu XY, et al. The kinase Jnk2 promotes stress-induced mitophagy by targeting the small mitochondrial form of the tumor suppressor ARF for degradation. Nat Immunol. 2015;16:458–66.
22.Samie M, Lim J, Verschueren E, Baughman JM, Peng I, Wong A, et al. Selective autophagy of the adaptor TRIF regulates innate inflammatory signaling. Nat Immunol. 2018;19:246–54.
23.Yao RQ, Li ZX, Wang LX, Li YX, Zheng LY, Dong N, et al. Single-cell transcriptome profiling of the immune space-time landscape reveals dendritic cell regulatory program in polymicrobial sepsis. Theranostics. 2022;12:4606–28.
24.Angus DC, Opal S. Immunosuppression and secondary infection in sepsis: part, not all, of the story. JAMA. 2016;315:1457–9.
25.Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:2594–605.
26.Reina-Campos M, Scharping NE, Goldrath AW. CD8+ T cell metabolism in infection and cancer. Nat Rev Immunol. 2021;21:718–38.
27.Velardi E, Tsai JJ, van den Brink MRM. T cell regeneration after immunological injury. Nat Rev Immunol. 2021;21:277–91.
28.Davenport MP, Smith NL, Rudd BD. Building a T cell compartment: how immune cell development shapes function. Nat Rev Immunol. 2020;20:499–506.
29.ElTanbouly MA, Noelle RJ. Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey. Nat Rev Immunol. 2021;21:257–67.
30.Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P, et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol. 2000;1:496–501.
31.Bolognese AC, Sharma A, Yang WL, Nicastro J, Coppa GF, Wang P. Cold-inducible RNA-binding protein activates splenic T cells during sepsis in a TLR4-dependent manner. Cell Mol Immunol. 2018;15:38–47.
32.Huang H, Wang S, Jiang T, Fan R, Zhang Z, Mu J, et al. High levels of circulating GM-CSF+CD4+ T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study. Cell Mol Immunol. 2019;16:602–10.
33.Singbartl K, Bockhorn SG, Zarbock A, Schmolke M, Van Aken H. T cells modulate neutrophil-dependent acute renal failure during endotoxemia: critical role for CD28. J Am Soc Nephrol. 2005;16:720–8.
34.Schmidt MV, Paulus P, Kuhn AM, Weigert A, Morbitzer V, Zacharowski K, et al. Peroxisome proliferator-activated receptor γ-induced T cell apoptosis reduces survival during polymicrobial sepsis. Am J Respir Crit Care Med. 2011;184:64–74.
35.Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8:776–87.
36.Tang D, Wang H, Billiar TR, Kroemer G, Kang R. Emerging mechanisms of immunocoagulation in sepsis and septic shock. Trends Immunol. 2021;42:508–22.
37.Abraham KJ, Khosraviani N, Chan JNY, Gorthi A, Samman A, Zhao DY, et al. Nucleolar RNA polymerase II drives ribosome biogenesis. Nature. 2020;585:298–302.
38.Bowman JC, Petrov AS, Frenkel-Pinter M, Penev PI, Williams LD. Root of the tree: the significance, evolution, and origins of the ribosome. Chem Rev. 2020;120:4848–78.
39.Darnell AM, Subramaniam AR, O'Shea EK. Translational control through differential ribosome pausing during amino acid limitation in mammalian cells. Mol Cell. 2018;71:229–43.e11.
40.Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136:731–45.
41.Quinternet M, Rothé B, Barbier M, Bobo C, Saliou JM, Jacquemin C, et al. Structure/function analysis of protein-protein interactions developed by the yeast Pih1 platform protein and its partners in box C/D snoRNP assembly. J Mol Biol. 2015;427:2816–39.
42.Marciniak SJ, Chambers JE, Ron D. Pharmacological targeting of endoplasmic reticulum stress in disease. Nat Rev Drug Discov. 2021;21:115–40.
43.Wang M, Kaufman RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature. 2016;529:326–35.
44.Khan MM, Yang WL, Wang P. Endoplasmic reticulum stress in sepsis. Shock. 2015;44:294–304.
45.Wang LX, Zhu XM, Luo YN, Wu Y, Dong N, Tong YL, et al. Sestrin2 protects dendritic cells against endoplasmic reticulum stress-related apoptosis induced by high mobility group box-1 protein. Cell Death Dis. 2020;11:125.
46.Wang LX, Ren C, Yao RQ, Luo YN, Yin Y, Wu Y, et al. Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells. Cell Mol Life Sci. 2021;78:8209–27.
47.Martín-Pérez R, Palacios C, Yerbes R, Cano-González A, Iglesias-Serret D, Gil J, et al. Activated ERBB2/HER2 licenses sensitivity to apoptosis upon endoplasmic reticulum stress through a PERK-dependent pathway. Cancer Res. 2014;74:1766–77.
48.Avivar-Valderas A, Salas E, Bobrovnikova-Marjon E, Diehl JA, Nagi C, Debnath J, et al. PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol. 2011;31:3616–29.
49.Rzymski T, Milani M, Pike L, Buffa F, Mellor HR, Winchester L, et al. Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene. 2010;29:4424–35.
50.Li JY, Ren C, Wang LX, Yao RQ, Dong N, Wu Y, et al. Sestrin2 protects dendrite cells against ferroptosis induced by sepsis. Cell Death Dis. 2021;12:834.
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