The induction of oral tolerance in early life requires the peripheral activation of long-lived RORγt+ regulatory T cells (Tregs) that develop in the colon. These cells are induced in response to microbiota and the loss of RORγt+ Tregs prior to weaning is associated with increased allergic responses as adults. These Tregs peak during the periweaning phase of life (around day of life 14–20), coinciding with luminal antigen translocation via goblet cell-associated antigen passages (GAPs). In our animal model, when GAPs form prematurely, in the neonatal phase, these mice display Treg instability and increased intestinal inflammation as adults. However, why colonic Treg development is limited to this time is unclear. Treg induction requires TGFβ and IL-2, and IL-2 is required for the maintenance of intestinal Tregs in adults. We have found distinct populations of cells produce IL-2 in the neonatal and periweaning colon. Among mononuclear phagocytic cells (MNPs) in the periweaning colon, a majority of the IL-2-producing RORγt+ MHCII+ populations are CX3CR1+ while a majority of these cells in the neonatal colon are CX3CR1–. This suggests IL-2+ MNPs in periweaning colons may be primarily epithelial-associated while those in neonatal mice are not. As RORγt+ MHCII+ antigen presenting cells have been shown as required for RORγt+ Treg induction, these results may suggest unique populations of IL-2-expressing cells capable of inducing Tregs in periweaning mice compared to neonatal mice.
Unique CX3CR1+ IL-2-producing mononuclear phagocytes in periweaning mice
Category
Poster and Podium (Block Symposium)
Description
Custom CSS
double-click to edit, do not edit in source
Date: May 5 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1