Lacc1, also known as C13orf31, is an enzyme highly expressed in inflammatory macrophages. It plays a central regulatory role in multiple inflammatory diseases such as inflammatory bowel diseases, arthritis, and microbial infections [1,2,3,4,5,6,7,8]. Biochemically, Lacc1 converts L-citrulline to L-ornithine and isocyanic acid, bridging proinflammatory nitric oxide synthase (NOS2) and polyamine immunometabolism [1,2].

In Lacc1 -/- mice, more severe colon lesions were observed after oral administration of Citrobacter rodentium, and an accelerated onset of arthritis and more severe inflammation occurred in collagen-induced arthritis and mannan-induced arthritis models, with increased serum and local TNF and elevated percentage of IL-17A-producing CD4+ T cells [6]. Lacc1 -/- mice also had more severe T-cell transfer colitis, increased bacterial burden in intestinal lymphoid organs, and altered T-cell cytokine levels [7]. Additionally, Lacc1 deletion aggravated dextran sodium sulfate (DSS)-induced inflammatory bowel disease in mice, with significant changes in the intestinal flora [8]. In human immune cells, LACC1 deficiency was associated with a novel form of genetically inherited juvenile arthritis linked to impaired autophagy in macrophages [3].

In conclusion, Lacc1 is crucial in regulating inflammation, bacterial clearance, and autophagy in macrophages. Gene knockout mouse models have revealed its important role in inflammatory bowel disease, arthritis, and other inflammatory diseases, providing insights into the mechanisms of these diseases and potential therapeutic targets.