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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1551547

Elevated levels of IRF1 and CASP1 as pyroptosis-related biomarkers for intestinal epithelial cells in Crohn's disease

Provisionally accepted
Xiaofang Xu Xiaofang Xu 1,2Xiaodan Lv Xiaodan Lv 2Ruizhi Zeng Ruizhi Zeng 3Zhixi Huang Zhixi Huang 2Ziqian 1102078101@qq.com Ziqian 1102078101@qq.com 2Bing Han Bing Han 2Guangfu Lin Guangfu Lin 2Jianing Lin Jianing Lin 2Shiquan Lin Shiquan Lin 2Junhua Fan Junhua Fan 2Xiaoping Lv Xiaoping Lv 2*
  • 1 Guangxi Medical University, Nanning, China
  • 2 Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
  • 3 Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Region, China

The final, formatted version of the article will be published soon.

    Crohn's disease (CD) is a complex inflammatory condition with the potential for severe complications. Pyroptosis is an inflammatory form of programmed cell death, and the role of pyroptosis in intestinal epithelial cells of CD remains unclear. In this study, pyroptosis-related hub genes were identified using datasets from the Gene Expression Omnibus database through differential expression analysis, machine learning algorithms, and single-cell sequencing analysis.Hub gene expression was validated using clinical samples and a trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model. Six pyroptosis-related hub genes (CASP1, IRF1, ZBP1, MLKL, MMP1, HTRA1) were identified. IRF1 and CASP1 exhibited significant upregulation in CD, including both colonic and ileal subtypes, with good diagnostic value across different CD subtypes.Additionally, these two genes were not elevated in any other intestinal disorders, except for ulcerative colitis. Single-cell sequencing analysis revealed a significant interaction between intestinal epithelial cells (IECs) and monocytes. The clinical samples further confirmed that the mRNA levels of IRF1 and CASP1 were significantly higher in CD patients compared to healthy controls.Additionally, the colitis rat model validated the upregulation of Irf1 and Casp1 at both mRNA and protein levels. Our findings identified IRF1 and CASP1 as critical pyroptosis-related biomarkers for IECs in CD, contributing to the understanding of pyroptosis in CD pathogenesis.

    Keywords: biomarkers, pyroptosis, intestinal epithelial cells, Crohn's disease, Bulk RNA sequencing, single-cell RNA sequencing

    Received: 25 Dec 2024; Accepted: 24 Jan 2025.

    Copyright: © 2025 Xu, Lv, Zeng, Huang, 1102078101@qq.com, Han, Lin, Lin, Lin, Fan and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiaoping Lv, Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Region, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.