鼻黏膜组织CD4+ T细胞参与季节性变应性鼻炎发病机制的生物信息学分析

doi:10.6040/j.issn.1673-3770.0.2023.130

摘要/Abstract

摘要： 目的探讨CD4⁺ T细胞参与季节性变应性鼻炎(seasonal allergic rhinitis, SAR)发生发展的关键生物学机制。方法获取基因表达数据库(gene expression omnibus, GEO)中GSE49782数据集的基因表达数据,使用GEO2R在线筛选该数据集中SAR患者基线水平及桦树花粉提取物激发后的鼻腔黏膜活检组织所分离提取的CD4⁺ T细胞之间的差异表达基因(differentially expressed genes, DEGs)。使用Metascape进行基因本体论(gene ontology, GO)及京都基因百科全书(kyoto encyclopedia of genes and genomes, KEGG)富集分析。通过STRING数据库分析DEGs所编码蛋白的相互作用,使用X2K查找DEGs与其相应转录因子之间的调控关系。结果以adj.P<0.05且|logFC|>0.585为标准共筛选出74个DEGs,其中包括8个上调基因和66个下调基因。GO和KEGG富集分析显示DEGs显著富集于细胞间连接、肌动蛋白丝束组装等相关的蛋白和通路。通过DEGs的蛋白-蛋白相互作用网络和转录因子分析进行进一步分析,筛选出5个核心DEGs(ASL、CTTN、EPS8、FNBP1L及 SH3KBP1)及SIN3A、CDK1和GSK3B等关键转录因子和重要激酶。结论鼻黏膜组织中的CD4⁺ T细胞可能通过ASL、CTTN、EPS8、FNBP1L及SH3KBP1核心DEGs及SIN3A、CDK1和GSK3B等关键转录因子和重要激酶调节细胞间连接等一系列生物学过程影响SAR的发生发展,为进一步深入理解SAR发生发展的分子生物学机制,探索其治疗的有效方案提供了新的见解及思路。

关键词: 季节性变应性鼻炎, CD4⁺ T细胞, 差异表达基因, 生物信息学分析

Abstract: Objective To explore the key biological mechanisms of CD4⁺ T cells involved in the pathogenesis of seasonal allergic rhinitis(SAR). Methods Gene expression data were obtained from the GSE49782 dataset in the Gene Expression Omnibus. GEO2R was used to screen the genes differentially expressed between CD4⁺ T cells isolated and extracted from nasal mucosa biopsy tissues of SAR patients before and after stimulation by a birch pollen extract. Metascape was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses. The STRING dataset was used to analyze the protein-protein interactions of differentially expressed genes(DEGs). X2K was used to explore the regulatory relationship between DEGs and their transcription factors. Results A total of 74 DEGs were screened based on an adjusted P-value of <0.05 and | logFC |>0.585. Of these DEGs, 8 were upregulated and 66 were downregulated. GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in proteins and pathways related to the intercellular junction and actin filament assembly. Through transcription factor analysis of DEGs and further analysis of the protein-protein interaction networks, five hubs of DEGs(ASL, CTTN, EPS8, FNBP1L, and SH3KBP1)as well as key transcription factors and important kinases(SIN3A, CDK1, and GSK3B)were found to play important roles in the pathogenesis of SAR. Conclusion CD4⁺ T cells in the nasal mucosa may affect the pathogenesis of SAR through a series of biological processes, for example, by regulating intercellular connections through their key expressed genes. The ASL, CTTN, EPS8, FNBP1L, and SH3KBP1 hubs of DEGs as well as key transcription factors and important kinases, such as SIN3A, CDK1, and GSK3B, could be involved in the occurrence and development of SAR. These novel findings will further our understanding of the molecular biological mechanism of SAR occurrence and development and will help in exploring effective therapeutic options.

Key words: Seasonal allergic rhinitis, CD4⁺ T cells, Differentially expressed genes, Bioinformatics analysis

中图分类号:

R765.21

侯凌霄,展长翠,许安廷,范新泰,王娜. 鼻黏膜组织CD4⁺ T细胞参与季节性变应性鼻炎发病机制的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 96-104.

HOU Lingxiao, ZHANG Changcui, XU Anting, FAN Xintai, WANG Na. Role of CD4⁺ T cells from nasal mucosa in the pathogenesis of patients with seasonal allergic rhinitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(4): 96-104.

参考文献

[1] Wheatley LM, Togias A. Allergic rhinitis[J]. N Engl J Med, 2015, 372(5): 456-463. doi:10.1056/nejmcp1412282
[2] Meltzer EO. Allergic rhinitis: burden of illness, quality of life, comorbidities, and control[J]. Immunol Allergy Clin North Am, 2016, 36(2): 235-248. doi:10.1016/j.iac.2015.12.002
[3] Bousquet J, Anto JM, Bachert C, et al. Allergic rhinitis[J]. Nat Rev Dis Primers, 2020, 6: 95. doi:10.1038/s41572-020-00227-0
[4] Wise SK, Damask C, Roland LT, et al. International consensus statement on allergy and rhinology: Allergic rhinitis - 2023[J]. Int Forum Allergy Rhinol, 2023, 13(4): 293-859. doi:10.1002/alr.23090
[5] Zhang Y, Lan F, Zhang L. Advances and highlights in allergic rhinitis[J]. Allergy, 2021, 76(11): 3383-3389. doi:10.1111/all.15044
[6] Zhang Y, Lan F, Zhang L. Update on pathomechanisms and treatments in allergic rhinitis[J]. Allergy, 2022, 77(11): 3309-3319. doi:10.1111/all.15454
[7] 黄嘉莉, 杨淑荣. 变应性鼻炎中信号传导通路的研究进展[J]. 山东大学耳鼻喉眼学报, 2020, 34(4): 125-129. doi:10.6040/j.issn.1673-3770.0.2019.355 HUANG Jiali, YANG Shurong. Advances in research on related signaling pathways in allergic rhinitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(4): 125-129. doi:10.6040/j.issn.1673-3770.0.2019.355
[8] Miura K, Inoue K, Ogura A, et al. Role of CD4⁺ T cells in allergic airway diseases: learning from murine models[J]. Int J Mol Sci, 2020, 21(20): 7480. doi:10.3390/ijms21207480
[9] Cosmi L, Maggi L, Santarlasci V, et al. T helper cells plasticity in inflammation[J]. Cytometry A, 2014, 85(1): 36-42. doi:10.1002/cyto.a.22348
[10] Seumois G, Ramírez-Suástegui C, Schmiedel BJ, et al. Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma[J]. Sci Immunol, 2020, 5(48): eaba6087. doi:10.1126/sciimmunol.aba6087
[11] Jin P, Zhang H, Zhu X, et al. Bioinformatics analysis of mRNA profiles and identification of microRNA-mRNA network in CD4⁺ T cells in seasonal allergic rhinitis[J]. J Int Med Res, 2022, 50(8): 3000605221113918. doi: 10.1177/03000605221113918
[12] 姜涛. 季节性过敏性鼻炎外周血CD4⁺T细胞基因测序数据挖掘及生物信息学分析[D]. 济南: 山东大学, 2022. doi:10.27272/d.cnki.gshdu.2022.003602 JIANG Tao. Bioinformatic analysis of RNA sequencing in peripheral CD4⁺ T cells of seasonal allergic rhinitis[D]. Jinan: Shandong University, 2022. doi:10.27272/d.cnki.gshdu.2022.003602
[13] 于克娜, 孙凯月, 张杰, 等. 西妥昔单抗治疗头颈部鳞状细胞癌差异表达基因的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(4): 117-124. doi:10.6040/j.issn.1673-3770.0.2020.189 YU Kena, SUN Kaiyue, ZHANG Jie, et al. Analysis of differentially expressed genes during cetuximab treatment of head and neck squamous cell carcinoma using bioinformatics[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(4): 117-124. doi:10.6040/j.issn.1673-3770.0.2020.189
[14] 李琳, 高正文, 崔楠, 等. 儿童慢性鼻窦炎基因表达谱的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 171-180. doi:10.6040/j.issn.1673-3770.0.2021.556 LI Lin, GAO Zhengwen, CUI Nan, et al. Bioinformatics analysis of gene expression profile in pediatric patients with chronic rhinosinusitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 171-180. doi:10.6040/j.issn.1673-3770.0.2021.556
[15] 顾瑜蓉, 李华斌. 《中国变应性鼻炎诊断和治疗指南(2022年,修订版)》解读[J]. 中国眼耳鼻喉科杂志, 2022, 22(2): 209-211. doi:10.14166/j.issn.1671-2420.2022.02.023 GU Yurong, LI Huabin. Interpretation of Chinese guideline for diagnosis and treatment of allergic rhinitis(2022, revision)[J]. Chinese Journal of Ophthalmology and Otorhinolaryngology, 2022, 22(2): 209-211. doi:10.14166/j.issn.1671-2420.2022.02.023
[16] Chen L, Shi L, Ma Y, et al. Hub Genes Identification in a Murine Model of Allergic Rhinitis Based on Bioinformatics Analysis[J]. Front Genet, 2020, 11: 970. doi: 10.3389/fgene.2020.00970
[17] Yan ZF, Liu LL, Jiao LL, et al. Bioinformatics analysis and identification of underlying biomarkers potentially linking allergic rhinitis and asthma[J]. Med Sci Monit, 2020, 26: e924934. doi:10.12659/MSM.924934
[18] Buckley A, Turner JR. Cell biology of tight junction barrier regulation and mucosal disease[J]. Cold Spring Harb Perspect Biol, 2018, 10(1): a029314. doi:10.1101/cshperspect.a029314
[19] Nur Husna SM, Tan HT, Shukri NM, et al. Nasal epithelial barrier integrity and tight junctions disruption in allergic rhinitis: overview and pathogenic insights[J]. Front Immunol, 2021, 12: 663626. doi:10.3389/fimmu.2021.663626
[20] Wan H, Winton HL, Soeller C, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions[J]. J Clin Invest, 1999, 104(1): 123-133. doi:10.1172/JCI5844
[21] 段甦, 韩新玲, 李颖, 等. 过敏性鼻炎鼻黏膜上皮紧密连接表达的研究[J]. 中国耳鼻咽喉头颈外科, 2021, 28(5): 293-296. doi:10.16066/j.1672-7002.2021.05.008 DUAN Su, HAN Xinling, LI Ying, et al. Study on the expression of tight junction of nasal mucosa epithelium in allergic rhinitis[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2021, 28(5): 293-296. doi:10.16066/j.1672-7002.2021.05.008
[22] 黄朝平, 张建辉, 朱力, 等. 紧密连接蛋白Claudin-1与变应性鼻炎发病机制相关性初探[J]. 中国眼耳鼻喉科杂志, 2014, 14(5): 283-286. doi:10.14166/j.issn.1671-2420.2014.05.033 HUANG Chaoping, ZHANG Jianhui, ZHU Li, et al. Correlation of claudin-1 and nosogenesis in allergic rhinitis[J]. Chinese Journal of Ophthalmology and Otorhinolaryngology, 2014, 14(5): 283-286. doi:10.14166/j.issn.1671-2420.2014.05.033
[23] 黄朝平, 张建辉, 朱力, 等. 紧密连接蛋白Occludin与变应性鼻炎发病机制相关性探讨[J]. 中国耳鼻咽喉颅底外科杂志, 2014, 20(4): 305-309. doi:10.11798/j.issn.1007-1520.201404005 HUANG Chaoping, ZHANG Jianhui, ZHU Li, et al. Effect of occludin on the pathogenesis of allergic rhinitis[J]. Chinese Journal of Otorhinolaryngology-skull Base Surgery, 2014, 20(4): 305-309. doi:10.11798/j.issn.1007-1520.201404005
[24] Song H, Wang YP, Shi CJ, et al. SH3KBP1 promotes glioblastoma tumorigenesis by activating EGFR signaling[J]. Front Oncol, 2020, 10: 583984. doi:10.3389/fonc.2020.583984
[25] Moss TJ, Qi Y, Xi L, et al. Comprehensive genomic characterization of upper tract urothelial carcinoma[J]. Eur Urol, 2017, 72(4): 641-649. doi:10.1016/j.eururo.2017.05.048
[26] Wang J, Zhang Y, Ma T, et al. Screening crucial lncRNAs and genes in osteoarthritis by integrated analysis[J]. Adv Rheumatol, 2023, 63(1): 7. doi: 10.1186/s42358-023-00288-1
[27] Lan F, Wang QQ, Zhang L. Gene transcriptome analysis of nasal epithelial cells in chronic rhinosinusitis with nasal polyps[J]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2021, 56(10): 1066-1072. doi:10.3760/cma.j.cn115330-20210422-00219
[28] Frittoli E, Matteoli G, Palamidessi A, et al. The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration[J]. Immunity, 2011, 35(3): 388-399. doi:10.1016/j.immuni.2011.07.007
[29] 张梓卉, 王振东, 白光宇, 等. Sin3A蛋白调节细胞功能综述[J]. 生命科学, 2015, 27(7): 892-897. doi:10.13376/j.cbls/2015122 ZHANG Zihui, WANG Zhendong, BAI Guangyu, et al. Sin3A regulates cell functions[J]. Chinese Bulletin of Life Sciences, 2015, 27(7): 892-897. doi:10.13376/j.cbls/2015122
[30] Peng LY, Li BB, Deng KB, et al. microRNA-214-3p facilitates M2 macrophage polarization by targeting GSK3B[J]. Kaohsiung J Med Sci, 2022, 38(4): 347-356. doi:10.1002/kjm2.12487
[31] 孙立薇, 刘子钰, 沙骥超, 等. 季节性与常年性变应性鼻炎鼻黏膜上皮细胞基因表达生物信息学分析[J]. 中华耳鼻咽喉头颈外科杂志, 2022, 57(4): 425-432. doi: 10.3760/cma.j.cn115330-20210630-00397 SUN Liwei, LIU Ziyu, SHA Jichao, et al. Bioinformatics analysis of nasal epithelial cell gene expression in seasonal and perennial allergic rhinitis[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2022, 57(4): 425-432. doi: 10.3760/cma.j.cn115330-20210630-00397
[32] Zhao L, Li YY, Li CW, et al. Increase of poorly proliferated p63+/Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps[J]. Allergy, 2017, 72(6): 975-984. doi:10.1111/all.13074

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