title: Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3⁺ regulatory T cells.
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.
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Pierson
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Cauwe
authors.forename: Antonia
authors.initials: A
authors.lastname: Policheni
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schlenner
authors.forename: Dean
authors.initials: D
authors.lastname: Franckaert
authors.forename: Julien
authors.initials: J
authors.lastname: Berges
authors.forename: Stephanie
authors.initials: S
authors.lastname: Humblet-Baron
authors.forename: Susann
authors.initials: S
authors.lastname: Schönefeldt
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Herold
authors.forename: David
authors.initials: D
authors.lastname: Hildeman
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Freitas
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Luther
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Daniel H D
authors.initials: DH
authors.lastname: Gray
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006706:Homeostasis / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2