Homeostatic control of regulatory T cell diversity

Regulatory T (T-Reg) cells constitute an essential counterbalance to adaptive immune responses. Failure to maintain appropriate T-Reg cell numbers or function leads to autoimmune, malignant and immunodeficient conditions. Dynamic homeostatic processes preserve the number of forkhead box P3-expressing (FOXP3(+)) T-Reg cells within a healthy range, with high rates of cell division being offset by apoptosis under steady-state conditions. Recent studies have shown that T-Reg cells become specialized for different environmental contexts, tailoring their functions and homeostatic properties to a wide range of tissues and immune conditions. In this Review, we describe new insights into the molecular controls that maintain the steady-state homeostasis of T-Reg cells and the cues that drive T-Reg cell adaptation to inflammation and/or different locations. We highlight how differing local milieu might drive context-specific T-Reg cell function and restoration of immune homeostasis, and how dysregulation of these processes can precipitate disease.