食管失弛缓症的先天免疫和适应性免疫失衡。

IF 3.3 3区 医学 Q2 CLINICAL NEUROLOGY
Journal of Neurogastroenterology and Motility Pub Date : 2023-10-30 Epub Date: 2023-08-16 DOI:10.5056/jnm21246
Lu Yao, Zuqiang Liu, Weifeng Chen, Jiaqi Xu, Xiaoyue Xu, Jiaxin Xu, Liyun Ma, Xiaoqing Li, Quanlin Li, Pinghong Zhou
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引用次数: 1

摘要

背景/目的:先前的研究表明,免疫介导的神经炎症在食管贲门失弛缓症的病因中起着关键作用。然而,对白细胞表型和比例的了解是有限的。本研究旨在评估食管失弛缓症患者白细胞和外周血单核细胞转录组的表型。方法:我们进行了高维流式细胞术来鉴定外周血白细胞亚群,并在食管下括约肌中进行了进一步的组织学验证。应用RNA测序技术研究贲门失弛缓症患者外周血单个核细胞的转录变化。通过估计RNA转录相对亚群进行细胞类型鉴定(CIBERSORT)用于估计免疫细胞类型。进行差异基因表达分析,并对差异表达的基因进行基因本体论、京都基因和基因组百科全书网络、蛋白质-蛋白质相互作用网络构建。结果:贲门失弛缓症患者出现先天免疫细胞和适应性免疫细胞失衡。具体而言,贲门失弛缓症患者外周血和食管下括约肌中的中性粒细胞和CD8+T细胞均增加。外周血嗜酸性粒细胞减少,但食管下括约肌大量浸润。外周血单核细胞RNA测序的CIBERSORT分析显示CD8+T细胞的患病率增加。在贲门失弛缓症中鉴定出170个失调基因,这些基因在免疫细胞迁移、免疫反应等方面富集。质子泵抑制剂分析揭示了这些基因的交叉点,并获得了贲门失弛弛缓症的7个枢纽基因,即IL-6、Toll样受体2、IL-1β、肿瘤坏死因子、补体C3和补体C1q A链。结论:贲门失弛缓症患者表现出系统先天免疫和适应性免疫失衡,这可能在贲门失弛弛缓症的发展中起着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Imbalance of Innate and Adaptive Immunity in Esophageal Achalasia.

Background/aims: Previous studies reveal that immune-mediated neuroinflammation plays a key role in the etiology of esophageal achalasia. However, the understanding of leucocyte phenotype and proportion is limited. This study aim to evaluate the phenotypes of leukocytes and peripheral blood mononuclear cells transcriptomes in esophageal achalasia.

Methods: We performed high-dimensional flow cytometry to identified subsets of peripheral leukocytes, and further validated in lower esophageal sphincter histologically. RNA sequencing was applied to investigate the transcriptional changes in peripheral blood mononuclear cells of patients with achalasia. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) was used for estimating the immune cell types. A differential gene expression analysis was performed and the differential expressed genes were subjected to gene ontology, Kyoto Encyclopedia of Genes and Genomes network, protein-protein interaction network construction.

Results: An imbalance between innate and adaptive immune cells occurred in achalasia. Specifically, neutrophils and CD8+ T cells increased both in peripheral blood and lower esophageal sphincter in achalasia. Eosinophils decreased in peripheral blood but massively infiltrated in lower esophageal sphincter. CIBERSORT analysis of peripheral blood mononuclear cells RNA sequencing displayed an increased prevalence of CD8+ T cells. 170 dysregulated genes were identified in achalasia, which were enriched in immune cells migration, immune response, etc. Proton pump inhibitor analysis revealed the intersections and gained 7 hub genes in achalasia, which were IL-6, Toll-like receptor 2, IL-1β, tumor necrosis factor, complement C3, and complement C1q A chain.

Conclusion: Patients with achalasia exhibited an imbalance of systematic innate and adaptive immunity, which may play an important role in the development of achalasia.

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来源期刊
Journal of Neurogastroenterology and Motility
Journal of Neurogastroenterology and Motility GASTROENTEROLOGY & HEPATOLOGY-CLINICAL NEUROLOGY
CiteScore
6.30
自引率
8.80%
发文量
96
期刊介绍: Journal of Neurogastroenterology and Motility (J Neurogastroenterol Motil) is a joint official journal of the Korean Society of Neurogastroenterology and Motility, the Thai Neurogastroenterology and Motility Society, the Japanese Society of Neurogastroenterology and Motility, the Indian Motility and Functional Disease Association, the Chinese Society of Gastrointestinal Motility, the South East Asia Gastro-Neuro Motility Association, the Taiwan Neurogastroenterology and Motility Society and the Asian Neurogastroenterology and Motility Association, launched in January 2010 after the title change from the Korean Journal of Neurogastroenterology and Motility, published from 1994 to 2009.
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