Imbalance of Innate and Adaptive Immunity in Esophageal Achalasia
- Author:
Lu YAO
1
;
Zuqiang LIU
;
Weifeng CHEN
;
Jiaqi XU
;
Xiaoyue XU
;
Jiaxin XU
;
Liyun MA
;
Xiaoqing LI
;
Quanlin LI
;
Pinghong ZHOU
Author Information
- Publication Type:Original Article
- From:Journal of Neurogastroenterology and Motility 2023;29(4):486-500
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
