For instance, RORγT+ Tregs have been shown to downregulate FoxP3 in the absence of IL-15 and become “ex-Tregs” that drive Th17-mediated colitis.54 It has also been shown that Th1 cells have the potential to upregulate FoxP3 to become T-bet+ Tregs.55,56 On the other hand, evidence from lineage tracking models, transfers and in vitro experiments suggest that T-bet+ Tregs are highly stable and retain FoxP3 expression independent of environmental conditions.21,57 Because of the stability of T-bet+ Tregs, plasticity is a less convincing explanation of reciprocity at later phases of infection. The gene discussed is FOXP3; the disease is colitis.