Endogenous retroelements promote tolerance to dietary antigens

Here, we reveal that constitutive endogenous retroelement expression promotes gut homeostasis and induction of oral tolerance to food. Notably, inhibition of reverse transcription prevents acquisition of oral tolerance to dietary antigens.

This phenomenon was associated with significant impact on regulatory T cell differentiation/accumulation and dendritic cell tolerogenic function. Mechanistically, retroelement responses to dietary antigens were controlled by innate sensing of retroelements via cGAS/STING pathway within gut epithelial cells. Altogether, our results propose that innate responses to retroelements control oral tolerance by acting as a local tonic signal required for Treg induction and differentiation, thereby promoting oral tolerance and preventing allergic responses to food.