It turns out that innate immune receptors, particularly those expressed in the gut, such as C-type lectin receptors (CLRs), are responsible for the development of IBD. However, the CLR also plays an important role in regulating the gut microbiota and protecting against pathogens. Therefore, balance is required to maintain intestinal homeostasis.
The dendritic cell immune receptor (DCIR) is one of the CLRs responsible for maintaining the homeostasis of the immune and skeletal systems. Previous studies have suggested that DCIR negatively regulates both innate and acquired immune responses. Thus, blocking DCIR could enhance immunity against colon tumours. However, its role in intestinal immunity remains unclear.
To this end, the team gave the mice water containing dextran sodium sulfate (DSS), a synthetic polysaccharide sulfate, and azoxymethane (AOM), a neurotoxic chemical, to induce tumors. colon is similar to that observed in people with IBD.
To their surprise, they found that the DCIR-deficient mice had reduced colitis severity and AOM-DSS-induced colorectal tumor growth. Furthermore, compared with wild-type (control) mice, DCIR-deficient mice showed lower body weight loss as well as decreased proinflammatory cell infiltration in the colon.
What do these observations imply? Professor Iwakura explains, “Our findings point to the fact that carcinogenesis and intestinal inflammation are facilitated by DCIR signaling, which suggests that blocking DCIR may prevent inflammation ulcerative colitis and colon cancer.”
Demonstrating this possibility, the study also revealed that using an antibody called “anti-NA2” against asialo-biantennary-N-glycans (NA2), a ligand (binding molecule) to DCIR , relieves symptoms of DSS colitis and suppresses the growth of colorectal tumors. .
The researchers were delighted by these findings. Speaking about the practical applications of their research, Professor Iwakura said, “Our results suggest that therapeutics targeting DCIR and its ligands can be used to treat effective treatment of autoimmune diseases, IBD and cancer, which are traditionally difficult to treat.”
Certainly, this study could open the door to new therapeutic strategies for the treatment of colorectal tumors, improving not only the lives of IBD patients but also our understanding of the underlying mechanisms. pathogenesis of human diseases.