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Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells
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Journal Article
Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells
2013
Overview
The signals controlling T
reg
cell homeostasis and survival are still being determined. Liston and colleagues demonstrate that peripheral T
reg
cells depend critically on IL-2 and the survival factor Mcl-1 but not on Bcl-2.
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 US,Nature Publishing Group
Subject
/ Animals
/ Female
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - metabolism
/ Male
/ Mice
/ Myeloid Cell Leukemia Sequence 1 Protein
/ Proto-Oncogene Proteins c-bcl-2 - genetics
/ Proto-Oncogene Proteins c-bcl-2 - metabolism
/ Survival
/ T cells
/ T-Lymphocytes, Regulatory - immunology
