Reg3b, a member of the Reg3 protein family, is an antimicrobial peptide containing a C-type lectin domain involved in carbohydrate binding [4]. It is expressed by intestinal epithelial cells and plays important roles in multiple biological processes. It is associated with mucosal-regenerative gp130 signalling and is involved in maintaining intestinal-barrier function. In addition, it may regulate some signalling pathways such as RAS-RAF-MEK-ERK and negatively regulate cytokine-induced activation of STAT3 [1,2,3].

In gene-knockout mouse models, Reg3b deficiency has diverse effects. In fructose-induced hepatosteatosis, activation of mucosal-regenerative gp130 signalling or expression of Reg3b counteracts fructose-induced barrier deterioration, endotoxaemia and subsequent lipogenesis [1]. In colitis-associated cancer, disruption of Bmi1 and Mel18 led to increased Reg3b expression, reducing polyp formation and tumour grade, indicating that Reg3b suppresses carcinogenesis [3]. In intestinal infections, Reg3b knockout mice showed higher numbers of viable Salmonella in the colon, mesenteric lymph nodes, spleen, and liver, suggesting its protective role against Salmonella enteritidis translocation but not against Listeria monocytogenes [4]. In dextran sulfate sodium-induced colitis, deletion of Reg3b exacerbated the disease, with increased body weight loss, neutrophil infiltration, and elevated expression of inflammatory cytokines [5].

In conclusion, Reg3b is crucial for maintaining intestinal-barrier integrity, has a protective role in intestinal infections and colitis, and suppresses carcinogenesis in colitis-associated cancer. Gene-knockout mouse models have been instrumental in revealing these functions of Reg3b in various disease-related biological processes.