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Updated: May 26, 2026
Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
Published on: September 18, 2016
Temporal genome expression profile analysis during t-cell-mediated colitis: identification of novel targets and
Kai Fang1, Songlin Zhang, John Glawe
1Department of Pathology, Louisiana State University Health Science Center, Shreveport, Louisiana 71103, USA.
Background:
T cells critically regulate inflammatory bowel disease (IBD), with T-cell-dependent experimental colitis models gaining favor in identifying potential pathogenic mechanisms; yet limited understanding of specific pathogenic molecules or pathways still exists.
Methods:
In this study we sought to identify changes in whole genome expression profiles using the CD4CD45Rbhi T-cell transfer colitis model compared to genome expression differences from Crohn's disease (CD) tissue specimens. Colon tissue was used for histopathological and genome expression profiling analysis at 0, 2, 4, or 6 weeks after adoptive T-cell transfer.
Results:
We identified 1775 genes that were significantly altered during disease progression, with 361 being progressively downregulated and 341 progressively upregulated. Gene expression changes were validated by quantitative real-time polymerase chain reaction (qRT-PCR), confirming genome expression analysis data. Differentially expressed genes were clearly related to inflammation/immune responses but also strongly associated with metabolic, chemokine signaling, Jak-STAT signaling, and angiogenesis pathways. Ingenuity network analysis revealed 25 unique network associations that were associated with functions such as antigen presentation, cell morphology, cell-to-cell signaling and interaction, as well as nervous system development and function. Moreover, many of these genes and pathways were similarly identified in CD specimens.
Conclusions:
These findings reveal novel, complex, and dynamic changes in gene expression that may provide useful targets for future therapeutic approaches.
Insights
This study reveals dynamic gene expression changes in experimental colitis, identifying altered inflammation and metabolic pathways. Many identified pathways were also found in Crohn's disease tissue, offering potential therapeutic targets.
Area of Science:
- Genomics
- Immunology
- Molecular Biology
Background:
- T cells play a critical role in inflammatory bowel disease (IBD) pathogenesis.
- Experimental colitis models are valuable for studying IBD mechanisms, but specific molecular targets remain elusive.
Purpose of the Study:
- To identify genome-wide expression profile changes in a T-cell transfer-induced colitis model.
- To compare these changes with gene expression profiles from Crohn's disease (CD) tissue.
Main Methods:
- Utilized a CD4CD45Rbhi T-cell transfer colitis model in mice.
- Analyzed colon tissue for histopathology and genome-wide expression profiling at multiple time points post-transfer.
- Validated gene expression changes using quantitative real-time polymerase chain reaction (qRT-PCR).
Main Results:
- Identified 1775 significantly altered genes during colitis progression (361 downregulated, 341 upregulated).
- Differentially expressed genes implicated inflammation, immune responses, metabolic pathways, chemokine signaling, Jak-STAT signaling, and angiogenesis.
- Network analysis revealed associations with antigen presentation, cell morphology, cell-cell signaling, and nervous system development; many findings mirrored those in CD specimens.
Conclusions:
- The study uncovered complex and dynamic gene expression alterations in experimental colitis.
- These findings highlight novel molecular pathways and potential therapeutic targets for IBD and Crohn's disease.
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