Lacc1, also known as C13orf31, is an enzyme highly expressed in inflammatory macrophages. It converts L-citrulline to L-ornithine and isocyanic acid, bridging proinflammatory nitric oxide synthase (NOS2) and polyamine immunometabolism. This function is central to its regulatory role in multiple inflammatory diseases such as inflammatory bowel diseases, arthritis, and microbial infections [1,2].

In Lacc1 -/- mice, more severe colon lesions were observed after oral administration of Citrobacter rodentium, and accelerated onset of arthritis and more severe inflammation occurred in collagen-induced arthritis models. Also, Lacc1 -/- mice had increased bacteria burden in intestinal lymphoid organs, more severe T-cell transfer colitis, and altered T-cell cytokine profiles. In macrophages, Lacc1 was required for toll-like receptor-induced bacteria uptake, reactive oxygen and nitrogen species production, and autophagy [3,4]. In a mouse model of inflammatory bowel disease, Lacc1 deletion aggravated disease, as seen by higher disease activity index scores, faster weight loss, and shorter colon lengths [5].

In conclusion, Lacc1 is essential for maintaining the balance between antibacterial defenses and intestinal inflammation, as well as regulating autophagy and T-cell cytokine responses. Gene knockout mouse models have been crucial in revealing its role in diseases like inflammatory bowel disease, arthritis, and microbial infections, highlighting its potential as a therapeutic target for these inflammation-related conditions.