中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (33): 8761-8777.doi: 10.12307/2026.484

• 组织构建细胞学实验 cytology experiments in tissue construction • 上一篇    下一篇

免疫细胞和儿童哮喘因果关系及炎症蛋白的介导作用

公佳璇，林  琳，王  淳，张星星，熊  英   

  1. 南京中医药大学针灸推拿学院·养生康复学院，江苏省南京市  210023
  • 收稿日期:2025-12-06 修回日期:2026-04-01 出版日期:2026-11-28 发布日期:2026-06-16
  • 通讯作者: 熊英，博士，教授，南京中医药大学针灸推拿学院·养生康复学院，江苏省南京市 210023
  • 作者简介:公佳璇，女，1999年生，河北省沧州市人，汉族，在读硕士，主要从事儿童推拿的临床与基础研究。
  • 基金资助:
    国家自然科学基金项目(81973970)，项目负责人：熊英

Causal relationships between immune cells and childhood asthma and the mediating role of inflammatory proteins

Gong Jiaxuan, Lin Lin, Wang Chun, Zhang Xingxing, Xiong Ying   

  1. School of Acupuncture-Moxibustion and Tuina, and School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
  • Received:2025-12-06 Revised:2026-04-01 Online:2026-11-28 Published:2026-06-16
  • Contact: Xiong Ying, PhD, Professor, School of Acupuncture-Moxibustion and Tuina, and School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
  • About author:Gong Jiaxuan, MS candidate, School of Acupuncture-Moxibustion and Tuina, and School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
  • Supported by:
     the National Natural Science Foundation of China, No. 81973970 (to XY)

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摘要：


文题释义：
儿童哮喘：是一种以慢性气道炎症和气道高反应性为特征的复杂呼吸系统疾病，核心病理机制为免疫系统异常激活导致气道炎症持续存在，引发可逆性气流受限及气道重塑。典型临床表现为反复发作的喘息、咳嗽、气促、胸闷等症状，常于夜间或凌晨加重。
孟德尔随机化：是一种基于遗传变异的因果推断方法，利用与暴露因素相关的遗传变异作为工具变量，在排除混杂因素和反向因果干扰的前提下，评估暴露因素对结局的因果效应。

背景：哮喘是儿童常见的慢性呼吸系统疾病之一，现有研究表明免疫细胞、炎症蛋白与儿童哮喘之间存在显著关联，但它们之间的具体因果关系尚不明确。
目的：探究炎症蛋白介导下免疫细胞与儿童哮喘的因果关系。
方法：应用免疫细胞、炎症蛋白全基因组关联研究汇总统计数据以及来源于FinnGen数据库的儿童哮喘数据进行双样本双向孟德尔随机化分析，探索这些变量之间的因果关系。逆方差加权法作为主要分析方法，Cochran’Q检验、MR-Egger截距检验和MR-PRESSO检验分别检测异质性、异常值和水平多效性。此外，采用中介分析确定炎症蛋白是否介导免疫细胞对儿童哮喘的影响。采用RT-qPCR和Western blot检测哮喘大鼠模型肺组织中中介炎症蛋白的表达。
结果与结论：①逆方差加权法分析结果显示，40种免疫细胞表型和7种炎症蛋白与儿童哮喘存在显著因果关联(P < 0.05)，均未发现存在反向关联的证据；②中介分析揭示白细胞介素33分别在2种免疫细胞(T细胞占白细胞总数的百分比、髓样树突状细胞表面CD86分子的表达水平)与儿童哮喘之间发挥中介作用，中介比例分别为12.7%和9.3%；③动物实验验证结果显示，与空白对照组相比，哮喘模型组大鼠肺组织中白细胞介素33 mRNA和蛋白表达显著升高(P < 0.01)；④蛋白质互作网络显示白细胞介素33与白细胞介素1受体样1等分子形成炎症调控枢纽，药物筛选发现Astegolimab等靶向药物的潜力。此项研究通过遗传学与实验验证相结合，阐明白细胞介素33是连接免疫细胞异常与儿童哮喘发病的核心炎症递质，借鉴国际多组学研究平台开发的生物信息学分析工具与算法模型，为优化适合中国人群遗传背景的变异解读流程、提升儿童哮喘病致病基因鉴定效率、探索儿童哮喘的生物学基础和早期干预疗法提供了新途径。
https://orcid.org/0009-0006-7877-5983 (公佳璇) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 儿童哮喘, 孟德尔随机化, 免疫细胞, 炎症蛋白, 中介分析, 逆方差加权法, 敏感性分析

Abstract: BACKGROUND: Asthma is one of the most prevalent chronic respiratory diseases in children. Existing studies have indicated significant associations among immune cells, inflammatory proteins, and childhood asthma, but the specific causal relationships remain unclear.
OBJECTIVE: To investigate the causal relationship between immune cells and childhood asthma mediated by inflammatory proteins.
METHODS: Utilizing data from the largest genome-wide association studies on immune cells, inflammatory proteins, and childhood asthma, we performed bidirectional two-sample Mendelian randomization analyses to explore the causal links between these variables. The inverse variance weighted method served as the primary analytical approach. Cochran’s Q test, MR-Egger intercept test, and MR-PRESSO were employed to assess heterogeneity, outliers, and horizontal pleiotropy, respectively. Mediation analysis was conducted to determine whether inflammatory proteins mediate the effect of immune cells on childhood asthma. Key inflammatory mediators were detected in an established asthmatic rat model using quantitative real-time PCR and western blot assay.
RESULTS AND CONCLUSION: (1) Inverse variance weighted analyses identified significant causal associations of 40 immune-cell phenotypes and 7 inflammatory proteins with childhood asthma (P < 0.05), but there was no evidence of reverse causality. (2) Mediation analysis revealed that interleukin-33 could play a mediating role between two types of immune cells (T cell %leukocyte and CD86 on myeloid dendritic cells) and childhood asthma, with mediating ratios of 12.7% and 9.3%, respectively. (3) Animal experiments verified that compared with the normal control group, the mRNA and protein levels of interleukin-33 in the lung tissue of rats in the asthma model group were significantly increased (P < 0.01). (4) Protein-protein interaction networks revealed that interleukin-33 and molecules such as interleukin-1 receptor-like 1 formed a pivotal hub in inflammation regulation, and drug screening revealed the potential of targeted therapies like Astegolimab. (5) By integrating genetics with experimental validation, this study establishes interleukin-33 as the pivotal inflammatory mediator linking immune-cell dysregulation to childhood asthma onset. Leveraging bioinformatic pipelines and algorithmic frameworks developed by international multi-omics platforms, we provide a new avenue for refining variant-interpretation workflows tailored to the Chinese population, improving the efficiency of asthma-susceptibility-gene identification, and elucidating the biological basis of childhood asthma for the development of early-intervention therapies.

Key words: childhood asthma, Mendelian randomization, immune cells, inflammatory proteins, mediation analysis, inverse variance weighted, sensitivity analysis 

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