The gut epithelial barrier is important to maintain intestinal homeostasis to protect from antigens, that exist in the lumen. When the epithelial barrier is weakened, bacterial translocation can progress, causing inflammatory bowel disease. The aryl hydrocarbon receptor (AhR) is an important environmental sensor that maintains the intestinal epithelial barrier. AhR ligands are diverse and largely classified into endogenous and exogenous ligands. The AhR exhibited different functions depending on the type of ligands. This study revealed the effects of endogenous and exogenous ligands on the proliferation of intestinal stem cells (ISC). 2,3,7,8tetrachlorodibenzo-ρ-dioxin (TCDD) was used as an exogenous ligand and 6Formylindolo[3,2-Ь] carbazole (FICZ) was used as an endogenous ligand. To investigate the function of AhR in intestinal epithelial cells, 3D culture was utilized to mimic the actual intestinal environment. It was found that FICZ decreased the growth of organoids, while TCDD did not exert such effects. Also, FICZ decreased the proliferation of ISC, whereas TCDD did not. Besides, TCDD disrupted the regulatory effects of FICZ on the organoids. In contrast to the results observed in organoids, in the in vivo system, FICZ increased the proliferating cells, while TCDD did not exhibit the same effect. These results indicated that under normal conditions, proliferation control by AhR ligands did not occur significantly. However, when the environment worsens, FICZ regulated epithelial cell proliferation while TCDD did not. Moreover, these findings implied that in the presence of cancer, the effect of AhR ligands on epithelial cells might differ, indicating that different effects on carcinogenesis depend on the type of AhR ligands.
