CAMP is a vital antimicrobial peptide that plays a protective role in immune regulation
New research is investigating how citrullination of cathelicidin (CAMP), mediated by peptidyl arginine deiminase 4 (PAD4), intensifies inflammatory bowel disease (IBD).
CAMP is a vital antimicrobial peptide that plays a protective role in immune regulation, pathogen defence, and the maintenance of the epithelial barrier.
IBD encompasses conditions such as Crohn’s disease (CD) and ulcerative colitis (UC), and is characterised by chronic inflammation of the gastrointestinal tract. Despite advancements in treatment, the mechanisms underlying IBD are still complex and poorly understood.
Recent research highlighted the role of antimicrobial peptides, such as CAMP, in modulating gut inflammation and microbiota balance. However, the post-translational modification of CAMP and its effect on IBD have not been fully explored; further investigation is needed to elucidate the exact role of CAMP modification in IBD and to determine potential therapeutic strategies.
Researchers from Changhai Hospital and Naval Medical University published “Citrullination of CAMP exacerbating mucosal inflammation in inflammatory bowel disease” in Precision Clinical Medicine, examining how citrullination of the antimicrobial peptide CAMP exacerbates inflammation in IBD.
The study found that PAD4-mediated citrullination of CAMP alters microbiota composition and immune cell responses, underscoring a pathway in IBD pathogenesis.
Using a dextran sodium sulfate (DSS)-induced colitis mouse model, researchers discovered that citrullination of CAMP, driven by PAD4, reduced its intestinal protein levels. This modification had no effect on CAMP transcription, but did lead to its degradation and diminished protective functions.
Metaproteomic analyses found 70 differentially expressed proteins and 15 altered microbiota families associated with CAMP deficiency. The absence of CAMP intensified intestinal inflammation, as evidenced by increased pro-inflammatory cytokine levels and disrupted epithelial barrier function.
The research also revealed that the citrullinated form of CAMP contributed to an imbalance in microbial communities, impacting arginine metabolism, and promoting dendritic cell (DC) maturation and Th17 polarisation. These findings highlight CAMP’s dual role in modulating the microbiota and regulating the immune response during IBD.
Dr Zhaoshen Li, one of the corresponding authors, said, “Understanding the post-translational modifications of antimicrobial peptide like CAMP provides critical insights into the complexities of IBD. By targeting PAD4-mediated citrullination, we may open new therapeutic avenues for improving the treatment and management of IBD.”
