P0050 4-Octyl Itaconate Protects Against Colitis by Modulating Neutrophil Function and Enhancing Intestinal Epithelial Barrier Integrity
Authors: Guo M , Lingjuan J , Ruan G , Runing Z , Yiqun G , Hong Y 
Published: January 2025

Background

Inflammatory bowel disease (IBD) is a complex gastrointestinal condition marked by immune system dysfunction and intestinal barrier damage. The pathogenesis involves a mix of genetic, environmental, and immunological factors, with the potential for itaconic acid derivatives like 4-Octyl itaconate (4-OI) to modulate immune responses and offer therapeutic benefits.

Methods

The study utilized a mouse model of acute colitis induced by dextran sulfate sodium (DSS) to evaluate the effects of 4-OI. C57BL/6J mice were divided into control and treatment groups, with interventions including 4-OI administration. Lamina Propria Mononuclear Cells (LPMC) isolation, flow cytometry, neutrophil studies, Western blot, qRT-PCR, and RNA-seq profiling were conducted to assess changes in immune cell populations, protein and gene expression, and global transcriptional responses.

Results

4-OI treatment resulted in the amelioration of DSS-induced colitis, evidenced by improved colonic epithelial barrier function, reduced secretion of pro-inflammatory factors, and dampened inflammatory signaling pathways. Notably, 4-OI reduced neutrophil infiltration and activity, including the formation of neutrophil extracellular traps (NETs), with minimal impact on T cells and macrophages. Moreover, we discovered that 4-OI primarily targeted the acute phase of the disease, with less satisfactory effects on alleviating chronic colitis models.

Conclusion

4-OI demonstrates potential as a therapeutic agent in acute colitis by preserving the intestinal epithelial barrier and modulating neutrophil activity. While the study provides evidence of 4-OI's effects on neutrophils and epithelial cells, further research is necessary to understand its mechanisms, particularly regarding chronic colitis and potential clinical applications.

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