ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1597528
This article is part of the Research TopicBiomarkers and Beyond: Predicting Course and Tailoring Treatment in Inflammatory Bowel DiseasesView all 17 articles
Multi-Omics Reveals Efferocytosis-Related Hub Genes as Biomarkers for Ustekinumab Response in Colitis
Provisionally accepted
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Defective efferocytosis in ulcerative colitis (UC) exacerbates inflammation due to impaired clearance of apoptotic cells, yet the molecular mechanisms linking efferocytosis-related genes to therapeutic outcomes remain unclear. This study aims to investigate the role of efferocytosis in UC and the key regulatory mechanism of efferocytosis. Methods: Multi-omics integration of single-cell and bulk transcriptomic data from human UC colonic mucosa identified efferocytosis-active cellular subpopulations. Machine learning algorithms screened hub genes, followed by molecular docking to assess interactions with UST. A mouse colitis model was used to verify the inflammatory damage of UC and the key genes that play the role in efferocytosis. Results: In UC, the "eat me" and "digest me" signaling pathways are predominantly upregulated in myeloid cells, while the "find me" signaling cascade shows marked activation in stromal cells. Macrophages characterized by the M2 polarization demonstrate enhanced phagocytic proficiency and are instrumental in the engulfment and clearance of apoptotic cells, thereby alleviating the inflammatory cascade in UC. Six hub genes (ANXA1, PANX1, ANXA5, CD93, SERPINE1, MFGE8) were associated with UC progression and correlated with clinical response to UST. Molecular docking analysis revealed strong binding affinities between these gene-encoded proteins and UST. Transcriptomic and proteomic analyses confirmed dysregulated expression of these hub genes in the colitis model. Conclusion: This study reveals cellular heterogeneity at different stages of efferocytosis in UC, identifies efferocytosis-related genes as critical regulators of mucosal repair and predictors of UST efficacy. Findings emphasize targeting macrophage-driven efferocytosis to resolve inflammation, offering novel strategies for improving treatment outcomes.
Keywords: Efferocytosis, ulcerative colitis, Multi-omics integration, Ustekinumab response, myeloid-stromal crosstalk
Received: 21 Mar 2025; Accepted: 30 Aug 2025.
Copyright: © 2025 Wang, Yuan, Xia and Liao. 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:
Jun-meng Wang, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Jing Yuan, Chengdu University of Traditional Chinese Medicine, Chengdu, 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.