Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells
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
Publisher's Version
https://doi.org/10.1038/ni.2649
NHMRC Grants
NHMRC/637353
Terms of Use/Rights Notice
© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Creation Date: 2013-09-01 12:00:00
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