Abstract
Oral tolerance (OT) towards antigens encountered in the gut is a vital immune function of gut immunity. Experimental models can demonstrate OT efficacy by feeding of a protein followed by peripheral immunization and measuring the specific antibody titer. We had previously shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a xenobiotic high-affinity aryl hydrocarbon receptor (AhR)-ligand, destabilized OT against ovalbumin (OVA) in mice. AhR is involved in the development, differentiation and function of immune cells, and highly expressed in gut epithelial cells and gut immune cells. We here used AhR-deficient mice to study the role of AhR in OT further. We show that complete AhR-deficiency undermines the stability of oral tolerance against OVA upon multiple immunizations, despite no renewed oral encounter with the antigen. This OT destabilization is accompanied by significant changes in IL10 and TGFβ RNA in the gut tissue. Using conditional AhR-deficient mouse lines, we identify T cells as the major responsible immune cell type in this context. Our findings add to knowledge that lack of AhR signaling in the gut impairs important gut immune functions.