Myeloid Cell Adhesion Molecule 1 (CADM1) Promotes Proinflammatory Signaling in Human Inflammatory Bowel Diseases

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Inflammatory bowel diseases (IBD) involve intestinal epithelial damage.
• Cytotoxic T cells are implicated in IBD pathogenesis.
• CADM1, a cell adhesion molecule, is upregulated in IBD colons.

Purpose of the Study:

• Investigate the role of CADM1 in IBD pathogenesis.
• Determine CADM1's function in myeloid cells.
• Evaluate CADM1 as a therapeutic target for IBD.

Main Methods:

• RNA sequencing of colon tissue from IBD and non-IBD (NIBD) patients.
• Functional characterization of soluble CADM1 (sCADM1) in lamina propria mononuclear cells (LPMCs).
• Generation of a myeloid-specific Cadm1 conditional knockout mouse model for chemical-induced colitis.

Main Results:

• CADM1 expression was enriched in macrophages and dendritic cells in IBD colons.
• Myeloid-specific Cadm1 deletion reduced T cell activation and protected mice from colitis.
• Administration of a CADM1-neutralizing antibody ameliorated colitis and protected intestinal epithelium.
• Elevated serum sCADM1 levels in IBD patients correlated with enhanced inflammatory STAT3 phosphorylation in LPMCs.

Conclusions:

• CADM1 acts as a mediator of pro-inflammatory signaling in the colon.
• CADM1 represents a potential therapeutic target for IBDs.