Functional dynamics of Foxp3⁺ regulatory T cells in mice and humans.

Forkhead box protein 3 (Foxp3)(+) regulatory T (Treg) cells are critical mediators for the establishment of self-tolerance and immune homeostasis and for the control of pathology in various inflammatory responses. While Foxp3(+) Treg cells often control immune responses in secondary lymphoid tissues, they must also traffic to and persist within non-lymphoid tissues, where they integrate various environmental cues to coordinate and adapt their effector acitvities in these sites. In recent years, our group has made use of several mouse models, including the non-obese diabetic model of type 1 diabetes, to characterize the factors, which impact the homeostasis, function, and reprogramming potential of Foxp3(+) Treg cells in situ. In addition, our recent work shows that Foxp3(+) Treg cells possess distinct post-transcriptional mechanisms of gene regulation, namely mRNA translation, to modulate tissue-specific inflammatory responses. In humans, there is a pressing need for reliable markers of FOXP3(+) Treg cells and their related function in blood and tissue. Experimental progress in our group has enabled us to discover novel markers of FOXP3(+) Treg cell (dys)function and unique gene signatures that discriminate effector and Treg cells, as well as functional and dysfunctional FOXP3(+) Treg cells.