Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells
- Author(s)
- Pierson, W; Cauwe, B; Policheni, A; Schlenner, SM; Franckaert, D; Berges, J; Humblet-Baron, S; Schonefeldt, S; Herold, MJ; Hildeman, D; Strasser, A; Bouillet, P; Lu, LF; Matthys, P; Freitas, AA; Luther, RJ; Weaver, CT; Dooley, J; Gray, DHD; Liston, A;
- Details
- Publication Year 2013-09,Volume 14,Issue #9,Page 959-965
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Foxp3(+) regulatory T (T-reg)cells are a crucial immunosuppressive population of CD4(+) T cells, yet the homeostatic processes and survival programs that maintain the T-reg cell pool are poorly understood. Here we report that peripheral T-reg cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2-dependent and costimulation-dependent process. By contrast, excess T-reg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-x(L) and Bcl-2 were dispensable for survival of T-reg cells, whereas Mcl-1 was critical for survival of T-reg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which T-reg cells maintain homeostasis via critical survival pathways.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- BH3-ONLY PROTEINS; DENDRITIC CELLS; IMMUNE-SYSTEM; LIFE-SPAN; HOMEOSTASIS; MICE; RECEPTOR; DEATH; AUTOIMMUNITY; TOLERANCE
- Research Division(s)
- Molecular Genetics Of Cancer; Immunology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128388/
- Publisher's Version
- https://doi.org/10.1038/ni.2649
- NHMRC Grants
- NHMRC/637353,
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Creation Date: 2013-09-01 12:00:00