对 CD11b+ 树突状细胞中 G 蛋白亚基γ 转导蛋白 2-自噬轴的生物信息学分析--它是哮喘内型中气道中性粒细胞炎症偏斜的潜在调节因子

IF 3.1 4区 医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2024-10-17 DOI:10.1002/iid3.70038
Xiaoying Ji, Yaoliang Zhou, Shendong He, Hongda Chen, Xianming Zhang, Zhifeng Chen, Jinwen Cai
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引用次数: 0

摘要

背景 哮喘是一种异质性炎症性疾病,有两种主要的临床内型:2 型(T2)高度哮喘和低度哮喘。树突状细胞(DCs)的可塑性和自噬作用会影响T辅助细胞(Th)2或Th17的分化,从而调节哮喘的内型。在过敏环境中,树突状细胞的自噬能力增强会促进Th2分化,而在致敏和感染环境中,自噬能力降低则有利于Th17细胞分化。直流电中的自噬调节涉及与各种途径的相互作用,如G蛋白偶联受体(GPCR)、哺乳动物雷帕霉素靶标(mTOR)或磷脂酰肌醇3-激酶(PI3K)途径。然而,影响哮喘内型的 DC 内特定分子仍不清楚。 方法 从基因表达总括(GEO)数据库中获取基因表达数据序列(GSE)64896、6858、2276 和 55247。使用 GEO2R 分析了 CD103+ 和 CD11b+ DCs 在卵清蛋白(OVA)和脂多糖(LPS)诱导后的差异表达基因(DEGs)。通过基因本体(GO)、京都基因与基因组百科全书(KEGG)和蛋白-蛋白相互作用(PPI)分析对DEGs进行了研究。利用STRING数据库和Cytoscape构建了中枢基因网络。使用学生 t 检验评估了 GSE6858、GSE2276 和 GSE55247 中 DCs 和所选中心基因的自噬差异。 结果 与 CD103+ DCs 相比,我们的分析在 CD11b+ DCs 中发现了 635 个上调基因和 360 个下调基因。这些DEG与 "PI3K-AKT信号通路"、"Ras信号通路 "等相关。研究发现了35个枢纽基因,其中CD11b+ DCs中的G蛋白亚基γ转导蛋白2(Gngt2)在类似于T2低哮喘模型的诱导环境下表现出相对特异性的表达增加,这与自噬缺陷有关。在 T2 高哮喘模型和对照组之间,肺部 Gngt2 的表达没有明显差异。 结论 我们的分析表明,在 T2 低哮喘小鼠模型中,Gngt2 是一种抑制自噬的适配器分子,通过 GPCR 通路促进 Th17 介导的气道炎症。针对这一途径的临床前研究提供了新的哮喘治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Bioinformatics analysis of G protein subunit gamma transduction protein 2-autophagy axis in CD11b+ dendritic cells as a potential regulator to skew airway neutrophilic inflammation in asthma endotypes

Background

Asthma is a heterogeneous inflammatory disease with two main clinical endotypes: type 2 (T2) high and low asthma. The plasticity and autophagy in dendritic cells (DCs) influence T helper (Th)2 or Th17 differentiation to regulate asthma endotypes. Enhanced autophagy in DCs fosters Th2 differentiation in allergic environments, while reduced autophagy favors Th17 cell differentiation in sensitized and infected environments. Autophagy regulation in DCs involves interaction with various pathways like G protein-coupled receptor (GPCR), mammalian target of rapamycin (mTOR), or phosphoinositide 3-kinase (PI3K) pathway. However, specific molecules within DCs influencing asthma endotypes remain unclear.

Methods

Gene expression data series (GSE) 64896, 6858, 2276, and 55247 were obtained from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CD103+ and CD11b+ DCs after induction by ovalbumin (OVA) and lipopolysaccharide (LPS) were analyzed using GEO2R. DEGs were examined through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses. The hub gene network was construct with STRING database and Cytoscape. Autophagy differences in DCs and the selected hub gene in GSE6858, GSE2276, and GSE55247 were evaluated using student t tests.

Results

Our analysis identified 635 upregulated and 360 downregulated genes in CD11b+ DCs, compared to CD103+ DCs. These DEGs were associated with “PI3K-AKT signaling pathway,” “Ras signaling pathway,” and so forth. Thirty-five hub genes were identified, in which G protein subunit gamma transduction protein 2 (Gngt2) in CD11b+ DCs exhibited a relatively specific increase in expression associated with autophagy defects under the induction environment similar to T2 low asthma model. No significant difference was found in lung Gngt2 expression between T2 high asthma model and control group.

Conclusion

Our analysis suggested Gngt2 acted as an adapter molecule that inhibited autophagy, promoting Th17-mediated airway inflammation via the GPCR pathway in a T2 low asthma mice model. Targeting this pathway provides new asthma treatment strategies in preclinical research.

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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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