切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2024, Vol. 10 ›› Issue (04) : 379 -383. doi: 10.3877/cma.j.issn.2096-1537.2024.04.011

综述

胸腺萎缩在脓毒症免疫紊乱中的研究进展
陈曦1,2, 吴宗盛1,2,3, 郑明珠1,2, 邱海波1,2,()   
  1. 1.210009 南京,江苏省重症医学重点实验室 东南大学附属中大医院重症医学科
    2.210009 南京,东南大学医学院
    3.210009 南京,江苏省重症医学重点实验室 东南大学附属中大医院急诊医学科
  • 收稿日期:2023-09-06 出版日期:2024-11-28
  • 通信作者: 邱海波
  • 基金资助:
    国家自然科学基金重点项目(81930058)国家自然科学基金项目(82171717)科技部国家重点研发计划项目(2020YFC083700)江苏省重症医学重点实验室项目(BM2020004)中央高校基本科研业务费专项资金项目(2242022K4007)

Research progress in sepsis immune disorder: thymic atrophy

Xi Chen1,2, Zongsheng Wu1,2, Mingzhu Zheng1,2, Haibo Qiu1,2,()   

  1. 1.Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China
    2.School of Medicine, Southeast University, Nanjing 210009, China
  • Received:2023-09-06 Published:2024-11-28
  • Corresponding author: Haibo Qiu
引用本文:

陈曦, 吴宗盛, 郑明珠, 邱海波. 胸腺萎缩在脓毒症免疫紊乱中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(04): 379-383.

Xi Chen, Zongsheng Wu, Mingzhu Zheng, Haibo Qiu. Research progress in sepsis immune disorder: thymic atrophy[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(04): 379-383.

脓毒症是危重症患者的重要死亡原因,免疫紊乱是脓毒症发生发展的关键。生理及病理状态下胸腺萎缩的发生均会损害机体的免疫功能。多项研究表明脓毒症会导致急剧的胸腺萎缩,主要表现为胸腺淋巴细胞的凋亡和胸腺上皮细胞的损伤增加,是脓毒症免疫功能紊乱的重要机制之一。更重要的是,胸腺功能的可逆性恢复可能与脓毒症患者预后密切相关。深入了解脓毒症时发生急性胸腺萎缩的机制并提出促进胸腺恢复的相关策略可能为脓毒症免疫治疗提供新的思路。

One of the major causes of death in critically ill patients is sepsis, which results from a dysregulated immune response to infection.Both physiological and pathological development of thymus atrophy impairs body immune function.Multiple studies have shown that sepsis also leads to dramatically thymic atrophy, mainly manifested by increased apoptosis of thymocytes and damage of thymic epithelial cells, which is one of the important mechanisms of immune dysfunction in sepsis.More importantly, reversible recovery of thymus function may be closely related to prognosis of sepsis patients.An in-depth understanding of the mechanisms of acute thymic atrophy in sepsis and the development of related strategies to promote thymic recovery may provide new insights for sepsis immunotherapy.

图1 脓毒症导致的胸腺萎缩机制及治疗示意图
1
Singer M, Deutschman CS, Seymour CW, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [J].JAMA, 2016, 315(8): 801.
2
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators.Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J].Lancet, 2018, 392(10159): 1789-1858.
3
van der Poll T, Shankar-Hari M, Wiersinga WJ.The immunology of sepsis [J].Immunity, 2021, 54(11): 2450-2464.
4
Conway Morris A, Datta D, Shankar-Hari M, et al.Cell-surface signatures of immune dysfunction risk-stratify critically ill patients:INFECT study [J].Intensive Care Med, 2018, 44(5): 627-635.
5
Drewry AM, Samra N, Skrupky LP, et al.Persistent lymphopenia after diagnosis of sepsis predicts mortality [J].Shock (Augusta, Ga.), 2014,42(5): 383-391.
6
Jiang J, Du H, Su Y, et al.Nonviral infection-related lymphocytopenia for the prediction of adult sepsis and its persistence indicates a higher mortality [J].Medicine, 2019, 98(29): e16535.
7
Xue M, Xie J, Liu L, et al.Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study [J].J Transl Med,2019, 17(1): 57.
8
Guidos C.Thymus and T-lymphocyte development: what is new in the 21st century? [J].Immunol Rev, 2006, 209(1): 5-9.
9
Kooshesh KA, Foy BH, Sykes DB, et al.Health consequences of thymus removal in adults [J].N Engl J Med, 2023, 389(5): 406-417.
10
van den Broek T, Borghans JAM, van Wijk F.The full spectrum of human naive T cells [J].Nat Rev Immunol, 2018, 18(6): 363-373.
11
Taub DD, Longo DL.Insights into thymic aging and regeneration [J].Immunol Rev, 2005, 205(1): 72-93.
12
Gustafson CE, Kim C, Weyand CM, et al.Influence of immune aging on vaccine responses [J].J Allergy Clin Immunol, 2020, 145(5): 1309-1321.
13
Zhang H, Weyand CM, Goronzy JJ.Hallmarks of the aging T-cell system [J].FEBS J, 2021, 288(24): 7123-7142.
14
Sauce D, Larsen M, Fastenackels S, et al.Evidence of premature immune aging in patients thymectomized during early childhood [J].J Clin Invest, 2009, 119(10): 3070-3078.
15
Gray DHD, Seach N, Ueno T, et al.Developmental kinetics, turnover,and stimulatory capacity of thymic epithelial cells [J].Blood, 2006,108(12): 3777-3785.
16
Savino W.The thymus is a common target organ in infectious diseases[J].PLoS Pathog, 2006, 2(6): e62.
17
Wang S, Huang K, Lin Y, et al.Sepsis-induced apoptosis of the thymocytes in mice [J].J Immunol, 1994, 152(10): 5014-5021.
18
Billard MJ, Gruver AL, Sempowski GD.Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses [J].PLoS One, 2011, 6(3): e17940.
19
Sommer N, Noack S, Hecker A, et al.Decreased thymic output contributes to immune defects in septic patients [J].J Clin Med, 2020,9(9): 2695.
20
Cabrera-Perez J, Condotta SA, James BR, et al.Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge [J].J Immunol, 2015, 194(4):1609-1620.
21
Hick RW, Gruver AL, Ventevogel MS, et al.Leptin selectively augments thymopoiesis in leptin deficiency and lipopolysaccharideinduced thymic atrophy [J].J Immunol, 2006, 177(1): 169-176.
22
Cuvelier P, Roux H, Couëdel-Courteille A, et al.Protective reactive thymus hyperplasia in COVID-19 acute respiratory distress syndrome[J].Crit Care, 2021, 25(1): 4.
23
Cardenas Palomo LF, de Souza Matos DC, Chaves Leal E, et al.Lymphocyte subsets and cell proliferation analysis in rabies-infected mice [J].J Clin Lab Immunol, 1995, 46(2): 49-61.
24
Wang D, Müller N, McPherson KG, et al.Glucocorticoids engage different signal transduction pathways to induce apoptosis in thymocytes and mature T cells [J].J Immunol, 2006, 176(3): 1695-1702.
25
Oberholzer C, Tschoeke SK, Moldawer LL, et al.Local thymic Caspase-9 inhibition improves survival during polymicrobial sepsis in mice [J].J Mol Med (Berl), 2006, 84(5): 389-395.
26
Tschoeke SK, Oberholzer C, LaFace D, et al.Endogenous IL-10 regulates sepsis-induced thymic apoptosis and improves survival in septic IL-10 null mice [J].Scand J Immunol, 2008, 68(6): 565-571.
27
Roggero E, Pérez AR, Tamae-Kakazu M, et al.Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection [J].J Endocrinol, 2006, 190(2): 495-503.
28
Chen W, Kuolee R, Austin JW, et al.Low dose aerosol infection of mice with virulent type A Francisella tularensis induces severe thymus atrophy and CD4+ CD8+ thymocyte depletion [J].Mol Microbiol,2005, 39(5-6): 189-196.
29
Kadouri N, Nevo S, Goldfarb Y, et al.Thymic epithelial cell heterogeneity:TEC by TEC [J].Nat Rev Immunol, 2020, 20(4): 239-253.
30
Zhou YJ, Peng H, Chen Y, et al.Alterations of thymic epithelial cells in lipopolysaccharide-induced neonatal thymus involution [J].Chin Med J (Engl), 2016, 129(1): 59-65.
31
Xu L, Wei C, Chen Y, et al.IL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection [J].Nat Commun, 2022, 13(1): 6881.
32
Wilkinson T, Dixon R, Page C, et al.ACCORD: a multicentre,seamless, phase 2 adaptive randomisation platform study to assess the efficacy and safety of multiple candidate agents for the treatment of COVID-19 in hospitalised patients: a structured summary of a study protocol for a randomised controlled trial [J].Trials, 2020, 21(1): 691.
33
Chaudhry MS, Velardi E, Dudakov JA, et al.Thymus: the next (re)generation [J].Immunol Rev, 2016, 271(1): 56-71.
34
Gruver AL, Sempowski GD.Cytokines, leptin, and stress-induced thymic atrophy [J].J Leukoc Biol, 2008, 84(4): 915-923.
35
Sportès C, Hakim FT, Memon SA, et al.Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets [J].J Exp Med, 2008, 205(7): 1701-1714.
36
Hennion-Tscheltzoff O, Leboeuf D, Gauthier SD, et al.TCR triggering modulates the responsiveness and homeostatic proliferation of CD4+thymic emigrants to IL-7 therapy [J].Blood, 2013, 121(23): 4684-4693.
37
Finch PW, Rubin JS.Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair [A]//Adv Cancer Res [M].Elsevier, 2004, 91: 69-136.
38
Wils EJ, Aerts-Kaya FSF, Rombouts EJC, et al.Keratinocyte growth factor and stem cell factor to improve thymopoiesis after autologous CD34+ cell transplantation in rhesus macaques [J].Biol Blood Marrow Transplant, 2012, 18(1): 55-65.
39
Redelman D, Welniak LA, Taub D, et al.Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network [J].Cell Immunol, 2008, 252(1-2):111-121.
40
Aiuti A, Tavian M, Cipponi A, et al.Expression of CXCR4, the receptor for stromal cell-derived factor-1 on fetal and adult human lymphohematopoietic progenitors [J].Eur J Immunol, 1999, 29(6):1823-1831.
41
Napolitano LA, Schmidt D, Gotway MB, et al.Growth hormone enhances thymic function in HIV-1-infected adults [J].J Clin Invest,2008, 118(3): 1085-1098.
42
Sutherland JS, Goldberg GL, Hammett MV, et al.Activation of thymic regeneration in mice and humans following androgen blockade [J].J Immunol, 2005, 175(4): 2741-2753.
43
Sutherland JS, Spyroglou L, Muirhead JL, et al.Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade [J].Clin Cancer Res, 2008, 14(4): 1138-1149.
[1] 庄燕, 戴林峰, 张海东, 陈秋华, 聂清芳. 脓毒症患者早期生存影响因素及Cox 风险预测模型构建[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(05): 372-378.
[2] 杨瑾, 刘雪克, 张媛媛, 金钧, 韦瑶. 肠道微生物来源石胆酸对脓毒症相关肝损伤的保护作用[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 265-274.
[3] 张霞, 张瑞, 郑志波, 张勤. 紫草素调控乳酸化修饰和线粒体功能改善脓毒症心肌病小鼠的预后[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 275-284.
[4] 张婧琦, 江洋, 孙佳璐, 唐兴喆, 赵宇飞, 崔颖, 李信响, 戴景月, 傅琳, 彭新桂. 基于肾周CT特征结合血清肌酐水平探讨脓毒症伴急性肾损伤的早期识别[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 285-292.
[5] 李振翮, 魏长青, 甄国栋, 李振富. 脓毒症并发急性呼吸窘迫综合征患者血清S1P、Wnt5a变化及其临床意义[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 293-300.
[6] 樊恒, 孙敏, 朱建华. 红景天苷通过抑制PI3K/AKT/mTOR信号通路对大鼠脓毒症急性肾损伤的保护作用[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(03): 188-195.
[7] 顾晓凌, 吴冠楠, 宋勇. 核因子E2相关因子2(Nrf2)与铁死亡在脓毒症相关急性肺损伤中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(02): 324-328.
[8] 杨翔, 郭兰骐, 谢剑锋, 邱海波. 转录组学在脓毒症诊疗中的临床研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(04): 384-388.
[9] 成人脓毒症患者β-内酰胺类抗生素延长输注专家共识编写组. 成人脓毒症患者β-内酰胺类抗生素延长输注专家共识[J/OL]. 中华重症医学电子杂志, 2024, 10(04): 313-324.
[10] 胡梓菡, 彭菲, 孙骎, 杨毅. 细胞外囊泡在脓毒症血管内皮损伤作用中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 265-270.
[11] 刘娟丽, 马四清, 乌仁塔娜. 髓源性抑制细胞在脓毒症中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 271-278.
[12] 苏生林, 马金兰, 于弘明, 杨晓军. 单细胞测序技术在脓毒症免疫研究中的应用进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 279-286.
[13] 陈惠英, 邱敏珊, 邵汉权. 脓毒症诱发肠黏膜屏障功能损伤的风险因素模型构建与应用效果[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 448-452.
[14] 傅新露, 李之岳, 卢丹. 妊娠合并结肠癌穿孔致脓毒症休克一例并文献复习[J/OL]. 中华产科急救电子杂志, 2024, 13(04): 227-231.
[15] 席静妮, 李娜, 张琪. 中性粒细胞与淋巴细胞比值对老年重症社区获得性肺炎进展为脓毒症的预测价值[J/OL]. 中华老年病研究电子杂志, 2024, 11(03): 28-31.
阅读次数
全文


摘要