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Title: Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells
Authors: Pierson, Wim ×
Cauwe, Bénédicte
Policheni, Antonia
Schlenner, Susan
Franckaert, Dean
Berges, Julien
Humblet-Baron, Stephanie
Schönefeldt, Susann
Herold, Marco J
Hildeman, David
Strasser, Andreas
Bouillet, Philippe
Lu, Li-Fan
Matthys, Patrick
Freitas, Antonio A
Luther, Rita J
Weaver, Casey T
Dooley, James
Gray, Daniel H D
Liston, Adrian #
Issue Date: Sep-2013
Publisher: Nature America Inc.
Series Title: Nature Immunology vol:14 issue:9 pages:959-65
Article number: 10.1038/ni.2649
Abstract: Foxp3(+) regulatory T (Treg) cells are a crucial immunosuppressive population of CD4(+) T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood. Here we report that peripheral Treg 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 Treg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-xL and Bcl-2 were dispensable for survival of Treg cells, whereas Mcl-1 was critical for survival of Treg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways.
URI: 
ISSN: 1529-2908
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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