河北医学2024，Vol.30Issue(2) ：218-223.DOI:10.3969/j.issn.1006-6233.2024.02.08

内质网磷酸化修饰与肺结核感染后免疫反应的相关性研究

Correlation Study of Endoplasmic Reticulum Phosphorylation Modification and Immune Response in Pulmonary Tuberculosis Infection

陈程 邓永 鲁学明 李榜龙 李小玉
河北医学2024，Vol.30Issue(2) ：218-223.DOI:10.3969/j.issn.1006-6233.2024.02.08
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内质网磷酸化修饰与肺结核感染后免疫反应的相关性研究

Correlation Study of Endoplasmic Reticulum Phosphorylation Modification and Immune Response in Pulmonary Tuberculosis Infection

陈程 1邓永 1鲁学明 1李榜龙 1李小玉1
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作者信息

  • 1. 湖南省长沙市第一医院, 湖南 长沙 410005
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摘要

目的:观察内质网(ER)磷酸化修饰与肺结核感染后免疫反应的相关性.方法:在这项观察性研究中,我们招募了2021 年1 月至2023 年6 月间在本院接受治疗的成年结核病患者(n=19)和没有结核病症状并接触过的家庭接触者(健康接触者)(n=20).所有患者在开始治疗前采集血样,并对这些血样进行了结核分枝杆菌特异性T细胞应答、细胞因子产生以及磷酸化的蛋白激酶样内质网激酶(PERK)和转录激活因子3(STAT3)表达的特征分析.结果:与健康接触者相比,结核病患者的 PPD 刺激的全血样品中IL-17、IL-22 水平显著降低(P<0.05),和IL-6、IL-10 水平显著增加(P<0.05).与健康接触者相比,结核病患者的自发 IL-10、IL-6 和 IFN-γ 浓度更高(P<0.05).在没有 IL-6 体外刺激的情况下,与健康接触者相比,结核病患者的CD4+ T 细胞中的 PERK 水平显著更高(P<0.001).加入IL-6 导致健康接触者CD4+ T细胞中PERK水平较没有IL-6 体外刺激健康接触者CD4+ T细胞显著增加(P<0.01).与健康接触者相比,结核病患者的CD4+ T细胞具有更高的STAT3 蛋白表达(P<0.05).在所有供体和结核病患者中,CD4+ T细胞中PERK和STAT3 表达之间呈显著正相关性(rho=0.571、0.503,均P<0.05).仅在结核病患者中观察到CD40L/IL-2 共表达 T 细胞和 CD40L/IFN-γ 共表达 T 细胞比例与STAT3 表达呈负相关(rho=-0.481、-0.705,P<0.001).结论:本研究提供了关于ER磷酸化修饰相关PERK/STAT3 信号通路可能驱动结核病患者中的免疫抑制/抗T细胞反应的证据.

Abstract

Objective:To observe the correlation between phosphorylation of endoplasmic reticulum(ER)and immune response after pulmonary tuberculosis infection.Methods:In this observational study,we recruited adult tuberculosis patients(n=19)who were treated in our hospital from January 2021 to June 2023 and family contacts(healthy contacts)who had no symptoms of tuberculosis(n=20).Blood samples were collected from all patients before treatment,and the characteristics of specific T cell response,cytokine pro-duction and expression of phosphorylated protein kinase-like endoplasmic reticulum kinase(PERK)and acti-vator of transcription 3(STAT3)of Mycobacterium tuberculosis were analyzed.Results:Compared with healthy contacts,the levels of IL-17 and IL-22 in whole blood samples stimulated by PPD in tuberculosis pa-tients decreased significantly(P<0.05),and the levels of IL-6 and IL-10 increased significantly(P<0.05).Compared with healthy contacts,the spontaneous concentrations of IL-10,IL-6 and IFN-γ in tubercu-losis patients were higher(P<0.05).In the absence of IL-6 stimulation in vitro,the level of PERK in CD4+ T cells of tuberculosis patients was significantly higher than that of healthy contacts(P<0.001).Adding IL-6 led to a significant increase in the level of PERK in CD4+ T cells of healthy contacts compared with those without IL-6 stimulation in vitro(P<0.01).Compared with healthy contacts,CD4+ T cells of tuberculosis patients had higher expression of STAT3 protein(P<0.05).In all donors and tuberculosis patients,there was a significant positive correlation between the expression of PERK and STAT3 in CD4+ T cells(rho=0.571,0.503,all P<0.05).The ratio of CD40L/IL-2 co-expressing T cells and CD40L/IFN-γ co-expressing T cells was negatively correlated with STAT3 expression only in tuberculosis patients(rho =-0.481,-0.705,P= 0.032,<0.001).Conclusion:This study provides evidence that the PERK/STAT3 signaling pathway relat-ed to ER phosphorylation modification may drive the immunosuppressive/antiproliferative T cell response in tu-berculosis patients.

关键词

内质网/T细胞/肺结核/磷酸化的蛋白激酶样内质网激酶/免疫反应

Key words

Endoplasmic reticulum/T cells/Pulmonary tuberculosis/Phosphorylated protein kinase-like endoplasmic reticulum kinase/Immune response

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基金项目

湖南省卫生健康委科研计划项目(202203082988)

出版年

2024
河北医学
河北省医学会

河北医学

CSTPCD
影响因子：1.915
ISSN：1006-6233
参考文献量16
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