Homeostatic control of regulatory T cell diversity.
Regulatory T (TReg) cells constitute an essential counterbalance to adaptive immune responses. Failure to maintain appropriate TReg cell numbers or function leads to autoimmune, malignant and immunodeficient conditions. Dynamic homeostatic processes preserve the number of forkhead box P3-expressing (FOXP3(+)) TReg cells within a healthy range, with high rates of cell division being offset by apoptosis under steady-state conditions. Recent studies have shown that TReg 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 TReg cells and the cues that drive TReg cell adaptation to inflammation and/or different locations. We highlight how differing local milieu might drive context-specific TReg cell function and restoration of immune homeostasis, and how dysregulation of these processes can precipitate disease.
1] Autoimmune Genetics Laboratory, VIB, Leuven 3000, Belgium. [2] Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium.
Adrian
A
Liston
1] The Walter and Eliza Hall Institute of Medical Research, Melbourne 3053, Australia. [2] Department of Medical Biology, University of Melbourne, Melbourne 3052, Australia.
Daniel H D
DH
Gray
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D014158:Transcription, Genetic
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors