Crohn’s disease and ulcerative colitis, collectively referred to as inflammatory bowel disease (IBD), are characterized by their prolonged inflammation of the gastrointestinal tract. IBD has been shown to lead to the development of colorectal tumors. To better understand the pathogenesis of IBD and the incidence of colorectal tumors, scientists at Tokyo University of Science (TUS) have shown that innate immune receptors, particularly those expressed in the gut, such as C-type lectin receptors (CLRs) , are responsible for the development of IBD.
While this finding provides an encouraging new therapy target for IBD and colorectal tumors, the researcher also notes that CLRs play a vital role in gut microbiota regulation and defense against pathogens. As a result, a balance must be struck to maintain intestinal homeostasis. Study results were published Aug. 2 in the journal Mobile Reports.
Dendritic cell immunoreceptor (DCIR) is one such CLR that is responsible for maintaining homeostasis of the immune system and skeletal system. Previous studies have suggested that DCIR negatively regulates both innate and acquired immune responses. Blocking DCIR could therefore potentially increase colon tumor immunity. However, its role in gut immunity has remained unclear.
For their study, the researchers fed the mice drinking water containing dextran sodium sulfate (DSS), a synthetic sulfated polysaccharide, and azoxymethane (AOM), a neurotoxic chemical, to induce intestinal tumors similar to those seen in people with IBD.
Surprisingly, the team found that the mice without DCIR showed reduced colitis severity and AOM-DSS-induced colorectal tumor growth. In addition, compared to the wild-type mice (control), the DCIR-deficient mice showed lower body weight loss and reduced pro-inflammatory cell infiltration in the colon.
“Our findings point to the fact that intestinal carcinogenesis and inflammation are facilitated by DCIR signaling, pointing to the possibility that blocking DCIR could prevent ulcerative colitis and colon cancer,” said study leaders Prof. Yoichiro Iwakura of TUS.
The study confirmed this possibility and further revealed that the use of an antibody called “anti-NA2” to asialo-biantennary-N-glycans (NA2), a ligand (binding molecule) to DCIR, reduced the symptoms of DSS colitis and the growth of colorectal tumors. .
Speaking about the practical applications of their study, Prof. Iwakura said, “Our results suggest that therapies targeting DCIR and its ligands can be used to effectively treat autoimmune diseases, IBD and cancer, which have traditionally been difficult to treat.”
The team noted that the study could open doors to new therapeutic strategies for treating colorectal tumors, improving not only the lives of patients with IBD, but also our understanding of the pathogenesis of human disease.