Frontiers in Immunology (Jan 2023)

Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn’s disease

  • Huihuan Wu,
  • Huihuan Wu,
  • Ruijie Zeng,
  • Ruijie Zeng,
  • Xinqi Qiu,
  • Kequan Chen,
  • Zewei Zhuo,
  • Kehang Guo,
  • Yawen Xiang,
  • Qi Yang,
  • Rui Jiang,
  • Felix W. Leung,
  • Qizhou Lian,
  • Weihong Sha,
  • Weihong Sha,
  • Hao Chen,
  • Hao Chen

DOI
https://doi.org/10.3389/fimmu.2022.1096587
Journal volume & issue
Vol. 13

Abstract

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IntroductionCrohn’s disease is characterized of dysregulated inflammatory and immune reactions. The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn’s disease remains largely unknown.MethodsThe microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn’s-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network.ResultsThe expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn’s disease. Moreover, consensus clustering identified two Crohn’s disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn’s disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn’s disease.ConclusionsOur findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn’s disease and might assist in the clinical decision-making process.

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