We show that TC IV numbers peak during the peri-weaning period and then rapidly decline. This wave of TCs is associated with a 7 fold-increase in the proportion of food-specific pTreg cells, suggesting that TC abundance determines the window of opportunity for oral tolerance 13/

Gut lymph nodes are critical for oral tolerance suggesting that these lymph nodes harbor a unique population of tolerogenic APCs. Excitingly, we found that TC IV are enriched in mesenteric lymph nodes, and virtually absent in non-gut lymph nodes. 10/

These mice were able to generate food-specific pTreg cells, indicating that TC IV is the pTreg-inducing subset. 9/

To address the role of Aire+ TCs in pTreg differentiation we generated a new mouse model to selectively ablate RORγt+Aire+ cells. These mice have a specific loss of Aire+ TCs (TC I and TC III) but TC IV numbers are not impacted. 8/

However, TC III express low levels of ITGB8, as well as Aire, and other studies have suggested that RORγt+ extra-thymic Aire-expressing cells (RORγt-eTACs) might be responsible for pTreg differentiation. 7/

Vanja and Yollanda started with a simple experiment – feeding mice fluorescently-labeled ovalbumin and seeing which cells in gut lymph nodes take up the protein. classical dendritic cells, they observed uptake by a specific subset of Thetis cells – TC IV. 5/

Although oral tolerance is often studied in adult mice, food allergies typically present in infancy when the immune system encounters food antigens for the first time. We therefore decided to study how tolerance is established during weaning. In mice this equates to day 12-18. 4/