August 2, 2022 -- Using mice models, researchers from Japan and China have shown that dendritic cell immunoreceptor (DCIR) protein deficiency is resistant to colonic tumors induced by dextran sodium sulfate (DSS) and azoxymethane (AOM), while identifying an antibody that reduces colitis severity and colonic tumor growth.
Their study, published online August 2 in the journal Cell Reports, highlights the potential of DCIR as a therapeutic target. Although previous studies have suggested that DCIR negatively regulates both innate and acquired immune responses and that blocking it could potentially boost immunity against colon tumors, its role in intestinal immunity has remained unclear.
In the study, mice were fed with drinking water containing DSS, a synthetic sulfated polysaccharide, and AOM, a neurotoxic chemical, to induce colon tumors similar to that observed in humans with inflammatory bowel disease (IBD).
Researchers found that mice lacking DCIR showed reduced colitis severity and colorectal tumor growth induced by AOM-DSS. Moreover, the DCIR-deficient mice showed lower body weight loss as well as reduced proinflammatory cell infiltration in the colon.
"Our findings point to the fact that intestinal carcinogenesis and inflammation are facilitated by DCIR signaling, which points to the possibility that blocking DCIR might prevent ulcerative colitis and colon cancer," Yoichiro Iwakura, professor at the Tokyo University of Science, said in a statement. "Our results suggest that therapeutics targeting DCIR and its ligands could be used to effectively treat autoimmune diseases, IBD, and cancer, which have been traditionally difficult to treat."