Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells.

Wim Pierson (1, 2) , Bénédicte Cauwe (1, 2) , Antonia Policheni (3, 4) , Susan M Schlenner (1, 2) , Dean Franckaert (1, 2) , Julien Berges (5) , Stephanie Humblet-Baron (1, 2) , Susann Schönefeldt (1, 2) , Marco J Herold (3, 4) , David Hildeman (6, 7) , Andreas Strasser (3, 4) , Philippe Bouillet (3, 4) , Li-Fan Lu (8) , Patrick Matthys (9) , Antonio A Freitas (5) , Rita J Luther (10) , Casey T Weaver (10) , James Dooley (1, 2) , Daniel H D Gray (3, 4) , Adrian Liston (1, 2)

1 Autoimmune Genetics Laboratory
2 Department of Microbiology & Immunology
3 The Walter & Eliza Hall Institute of Medical Research
4 Department of medical Biology
5 Biologie des Populations Lymphocytaires
6 Children's Hospital Medical Center
7 Division of Immunobiology
8 Section of molecular Biology, Division of Biological Sciences
9 Laboratory of Immunobiology, Rega Institute
10 Department of Pathology

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.

Domains: Life Sciences [q-bio]; Immunology

Wim Pierson, Bénédicte Cauwe, Antonia Policheni, Susan M Schlenner, Dean Franckaert, et al.. Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells.. Nature Immunology, 2013, 14 (9), pp.959-65. ⟨10.1038/ni.2649⟩. ⟨pasteur-00853340⟩