Integrated transcriptomic and proteomic profiling of colonic tissue in interleukin-10-deficient mice.

Introduction

A study published by Li et al. in Scientific Data (Nature), in 2025 detailed comprehensive molecular characterisation of chronic colitis in interleukin-10–deficient (IL-10⁻/⁻) mice, a model widely recognised for its relevance to Crohn’s disease-like pathology. By integrating RNA based profiling with label free protein quantification, the study aimed to clarify how IL-10 loss reshapes the biological landscape of the inflamed colon. Because IL-10 governs immune tolerance and mucosal homeostasis, its absence induces broad disruptions across immune and epithelial compartments. The identification of several hundred altered genes, including strong induction of inflammatory mediators and suppression of epithelial function genes, alongside extensive proteomic changes created a rich dataset for exploring disease associated pathways. This integrated approach strengthens the interpretability of the findings, enabling a cohesive view of inflammation related mechanisms. The work adds meaningful depth to the understanding of IL-10 driven pathology and provides a resource that can support both mechanistic studies and therapeutic hypothesis generation in inflammatory bowel disease.

Main Points

• IL-10⁻/⁻ knockout mice were aged to allow the spontaneous development of a chronic colitis, characterised by established inflammatory pathology within the colon, including immune cell infiltration and disruption of normal tissue architecture. Once disease was established, colonic  tissue was harvested and directly compared with tissue from age matched wild-type control mice. This experimental design ensured that observed molecular differences reflected IL-10 deficiency driven inflammation rather than age-related variation.
• RNA was isolated from colonic tissue and subjected to high throughput sequencing to assess global transcriptional changes associated with chronic inflammation. In parallel, matched samples were analysed using label free proteomic approaches to quantify corresponding changes at the protein level. Differential expression analyses enabled identification of several hundred genes and pathways significantly altered in IL-10⁻/⁻ mice relative to controls, with pronounced upregulation of immune and inflammation-associated transcripts in the IL-10⁻/⁻ mice. Pro-inflammatory cytokines such as IL-1β and TNF were strongly induced, alongside increased expression of IFN-ϒ and interferon-responsive genes, indicating sustained inflammatory signalling.
• The differentially expressed genes revealed alterations across immune, metabolic, and epithelial pathways, providing a coherent biological narrative for the development of spontaneous colitis in these mice. Chemokines involved in leukocyte recruitment, including CXCL1 and CXCL2, were among the most highly induced transcripts, consistent with extensive immune cell infiltration. In contrast, genes associated with epithelial integrity and intestinal homeostasis, including ALPI and multiple solute carrier (SLC) family members, were broadly downregulated, reflecting impaired barrier and metabolic function.The sequencing output demonstrated strong consistency across biological replicates, and the downstream processing pipeline applied well established analytical tools to ensure accurate quantification of gene expression differences. High quality RNA isolation, mRNA enrichment, controlled cDNA synthesis, and indexed library construction ensured reliable input for sequencing. The resulting gene level insights complemented the proteomic measurements, which added an additional layer of validation and context. Although extended discussion of the concordance between RNA and protein alterations was limited, the complementary nature of the datasets enhanced confidence in the biological patterns observed. 

Conclusion

This integrated molecular analysis of IL-10 deficient colitis offered valuable insight into the pathways disrupted during chronic intestinal inflammation. Transcriptomic profiling revealed pronounced immune activation alongside suppression of epithelial and metabolic gene programs, deepening the understanding of IL-10’s role in mucosal regulation. While additional exploration of relationships between RNA and protein changes could further strengthen the interpretation, the findings presented a compelling and informative resource for advancing research into inflammatory bowel disease research and for highlighting the power of RNA based discovery in IL-10 models.

EPISTEM SERVICES

What we do

Epistem offers more than 25 years of experience in gastrointestinal biology, including 15 years running models that replicate aspects of IBD in humans and can be used to generate target validation and mechanism of action data to confirm the efficacy of novel therapeutic agents.

IBD

We offer acute models of IBD using DSS and chronic models using cycles of DSS, the IL10^-/-  mouse model as described in this paper, Rag2^-/- mice, and adoptive T-cell transfer models. Readouts include Disease Activity Index, large bowel weight:length ratio, immune cell phenotyping, multiplex cytokine analysis, faecal lipocalin 2, MPO activity, quantitative histology and immunohistochemistry.

NGS

We regularly employ multiomic assessment studies which cover a wide spectrum of tissues and cells. We offer qPCR and NGS services for gene expression, whole exome and epigenetic analysis in all species. This is complemented by powerful bioinformatic analysis to create robust gene-signatures for biomarker discovery.

Epistem has a long history of evaluating a broad range of potential therapeutics with differing mechanisms of action and routes of delivery. All studies can be conducted in comparison to standard of care agents.