ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1622744
This article is part of the Research TopicIntestinal microenvironment and autoimmune diseasesView all 5 articles
PD-L1 Deficiency Exacerbates Colitis Severity by Remodeling Gut Microbiota in Inflammatory Bowel Disease
Provisionally accepted
- 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China
- 2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
- 3NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- 4Department of Immunology, School of Cell and Gene Therapy, Songjiang Research Institute, Shanghai Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Inflammatory bowel disease (IBD) is a chronic autoimmune disorder driven by gut microbiota dysbiosis. As an essential immune checkpoint, Programmed death-ligand 1 (PD-L1) has been implicated in modulating gut microbiota composition. However, the precise role of PD-L1 in shaping metagenomic profiles during IBD-associated colitis remains unexplored.DSS-induced colitis was established in both PD-L1 knockout (Pdcd1lg1-/-) mice and wild-type (wt) control mice. Clinical parameters, including disease activity index (DAI), body weight changes, colon length, and histopathological alterations, were systematically evaluated using non-parametric Kruskal-Wallis tests and ANOVA to compare colitis severity between genotypes.PD-L1 knockout mice exhibited exacerbated colitis, manifesting significantly greater weight loss (p<0.05 vs. wt_DSS), colonic shortening (p<0.05), and DAI scores (p<0.05) and inflammatory changes. PD-L1 knockout mice showed distinct dysbiosis, with enriched pathobionts (Escherichia coli, p=0.006; Bacteroides thetaiotaomicron, p=0.015) and depletion of commensals (Tritrichomonas foetus, p<0.001; Ligilactobacillus murinus). Alpha diversity analysis using Chao1 index revealed statistically significant differences between experimental groups (p=0.05). The transporters downregulate anti-inflammatory SCFA metabolism. KEGG enrichment analysis of differentially expressed genes (DEGs) revealed significant associations with immune and inflammatory pathways in PD-L1 knockout mice.PD-L1 deficiency aggravates colitis by driving pathogenic microbiota alterations and impairing microbial metabolic homeostasis, highlighting its dual regulatory roles in immune homeostasis and microbiome dynamics.
Keywords: programmed death ligand 1 (PD-L1), Gut Microbiota, Metagenomic analysis, Autoimmunity, Inflammatory bowel disease (IBD)
Received: 04 May 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Ma, Suo, Sheng and Chen. 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: Ling Chen, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China
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