Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Juvenile inflammatory bowel disease (IBD) presents unique challenges in understanding disease mechanisms.
• The role of Tarm1 in pediatric IBD and its impact on intestinal barrier integrity remains largely unexplored.

Purpose of the Study:

• To investigate the function of Tarm1 in a dextran sulfate sodium (DSS)-induced colitis model in juvenile mice.
• To elucidate the mechanisms by which Tarm1 influences intestinal barrier function during pediatric colitis.

Main Methods:

• Established a DSS-induced colitis model in 4-week-old juvenile mice.
• Assessed disease activity and histopathology via H&E staining.
• Quantified Tarm1, F4/80, CD68, and CD86 expression using qPCR, Western blotting, and immunofluorescence.
• Measured trans epithelial electric resistance (TEER) to evaluate intestinal barrier function.

Main Results:

• Juvenile mice with DSS-induced colitis exhibited increased colonic Tarm1 expression, elevated macrophage M1 polarization, and heightened pro-inflammatory cytokines.
• These mice also displayed significant impairment of the intestinal mucosal barrier.
• Tarm1 knockdown in RAW264.7 cells suppressed lipopolysaccharide (LPS)-induced M1 polarization and mitigated barrier damage in co-cultured intestinal cells.

Conclusions:

• Tarm1 expression is upregulated in the colonic tissues of juvenile mice suffering from colitis.
• Reducing Tarm1 expression in macrophages attenuated LPS-induced M1 polarization and intestinal barrier damage.
• Targeting Tarm1 presents a promising therapeutic strategy for pediatric inflammatory bowel disease.