Distinct contributions of cathelin-related antimicrobial peptide (CRAMP) derived from epithelial cells and macrophages to colon mucosal homeostasis.

The cathelin-related antimicrobial peptide CRAMP protects the mouse colon from inflammation, inflammation-associated carcinogenesis, and disrupted microbiome balance, as shown in systemic Cnlp-/- mice (also known as Camp-/- mice). However, the mechanistic basis for the role and the cellular source of CRAMP in colon pathophysiology are ill defined. This study, using either epithelial or myeloid conditional Cnlp-/- mice, demonstrated that epithelial cell-derived CRAMP played a major role in supporting normal development of colon crypts, mucus production, and repair of injured mucosa. On the other hand, myeloid cell-derived CRAMP potently supported colon epithelial resistance to bacterial invasion during acute inflammation with exacerbated mucosal damage and higher rate of mouse mortality. Therefore, a well concerted cooperation of epithelial- and myeloid-derived CRAMP is essential for colon mucosal homeostasis.