PMID- 36685554 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230201 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn's disease. PG - 1096587 LID - 10.3389/fimmu.2022.1096587 [doi] LID - 1096587 AB - INTRODUCTION: Crohn'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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: Our 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. CI - Copyright (c) 2023 Wu, Zeng, Qiu, Chen, Zhuo, Guo, Xiang, Yang, Jiang, Leung, Lian, Sha and Chen. FAU - Wu, Huihuan AU - Wu H AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. AD - School of Medicine, South China University of Technology, Guangzhou, China. FAU - Zeng, Ruijie AU - Zeng R AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. AD - School of Medicine, Shantou University Medical College, Shantou, China. FAU - Qiu, Xinqi AU - Qiu X AD - Zhuguang Community Healthcare Center, Guangzhou, China. FAU - Chen, Kequan AU - Chen K AD - Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Zhuo, Zewei AU - Zhuo Z AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Guo, Kehang AU - Guo K AD - Department of Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Xiang, Yawen AU - Xiang Y AD - Edinburgh Medical School, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom. FAU - Yang, Qi AU - Yang Q AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Jiang, Rui AU - Jiang R AD - School of Medicine, South China University of Technology, Guangzhou, China. FAU - Leung, Felix W AU - Leung FW AD - David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States. FAU - Lian, Qizhou AU - Lian Q AD - Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China. FAU - Sha, Weihong AU - Sha W AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. AD - School of Medicine, South China University of Technology, Guangzhou, China. FAU - Chen, Hao AU - Chen H AD - Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. AD - School of Medicine, South China University of Technology, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230105 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) SB - IM MH - Humans MH - *Inflammasomes/metabolism MH - *Crohn Disease/genetics/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism PMC - PMC9849378 OTO - NOTNLM OT - Crohn's disease OT - NLRP3 inflammasome OT - drug OT - immune landscape OT - treatment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HY declared a shared parent affiliation with the author, KC, to the handling editor at the time of the review. EDAT- 2023/01/24 06:00 MHDA- 2023/01/25 06:00 PMCR- 2022/01/01 CRDT- 2023/01/23 04:38 PHST- 2022/11/12 00:00 [received] PHST- 2022/12/02 00:00 [accepted] PHST- 2023/01/23 04:38 [entrez] PHST- 2023/01/24 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1096587 [doi] PST - epublish SO - Front Immunol. 2023 Jan 5;13:1096587. doi: 10.3389/fimmu.2022.1096587. eCollection 2022.