REGULATION OF COLONIC MACROPHAGES AND TYPE-17 AND REGULATORY T CELLS IN DSS-COLITIS BY IBD-ASSOCIATED TRANSCRIPTION...

Area of Science:

• Immunology
• Genetics
• Gastroenterology

Background:

• Genome-wide association studies identified cAMP-responsive element modulator (CREM) gene polymorphisms influencing diarrheal disease susceptibility.
• CREM is a transcription factor involved in genetic and epigenetic regulation.
• CREM polymorphisms are linked to inflammatory bowel disease (IBD) susceptibility, suggesting a role in enteric inflammation.

Purpose of the Study:

• To investigate the role of CREM in the context of chemically induced colitis.
• To determine if global or intestinal epithelial cell-specific deletion of CREM impacts colitis severity.

Main Methods:

• Mice with tamoxifen-inducible global or intestinal epithelial cell (IEC)-specific deletion of CREM were generated.
• Colitis was induced using dextran-sodium sulfate (DSS).
• Mice were assessed for weight loss, clinical scores, immune cell populations via flow cytometry, and gut microbiota via sequencing.

Main Results:

• Global deletion of CREM significantly ameliorated DSS-colitis severity, reducing weight loss and clinical scores.
• Intestinal epithelial cell-specific deletion of CREM did not replicate this protective effect.
• CREM deletion was associated with increased colonic macrophages, RORγt+ regulatory T cells (pTregs), and T helper 17 (Th17) cells.

Conclusions:

• Global deletion of CREM reduces DSS-colitis severity.
• The protective mechanism involves increased macrophages and specific T cell populations in the colon.
• Further research will elucidate CREM's immunoregulatory role in intestinal inflammation to identify potential therapeutic targets for IBD.