Major functions of intestinal-resident Tregs in the regulation of epithelial SCs. Several subpopulations of Tregs have been reported in the intestines with distinct roles in mediating tolerance towards dietary antigens and microbiota. Namely, RORγt- Tregs appear to be responsible for mediating dietary tolerance; RORγt + Tregs mediate microbial tolerance; whereas Gata3+ Tregs respond to the epithelial-derived interleukin-33, suggesting a possibility that they mediate epithelial-immune crosstalk. Indeed, IL-33 induces the production of anti-inflammatory cytokines TGFβ and IL-10 in Tregs. Finally, naïve T cells differentiated towards a Treg-like phenotype (iTreg, induced Tregs) by administration of TGFβ, support ISC growth in vitro by secretion of IL-10. Brown arrows indicate findings from in vitro studies.