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

作者：Pierson Wim; Cauwe Benedicte; Policheni Antonia; Schlenner Susan M; Franckaert Dean; Berges Julien; Humblet Baron Stephanie; Schonefeldt 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^*

来源：Nature Immunology, 2013, 14(9): 959-+.

DOI：10.1038/ni.2649

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.

• 出版日期2013-9
• 单位河北医科大学