title: Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo.
abstract: Survival of various immune cell populations has been proposed to preferentially rely on a particular anti-apoptotic BCL-2 family member, for example, naive T cells require BCL-2, while regulatory T cells require MCL-1. Here we examined the survival requirements of multiple immune cell subsets in vitro and in vivo, using both genetic and pharmacological approaches. Our findings support a model in which survival is determined by quantitative participation of multiple anti-apoptotic proteins rather than by a single anti-apoptotic protein. This model provides both an insight into how the sum of relative levels of anti-apoptotic proteins BCL-2, MCL-1 and A1 influence survival of T cells, B cells and dendritic cells, and a framework for ascertaining how these different immune cells can be optimally targeted in treatment of immunopathology, transplantation rejection or hematological cancers.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Carrington
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Brady
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Sutherland
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Anstee
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Schenk
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Ingela B
authors.initials: IB
authors.lastname: Vikstrom
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Delconte
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Segal
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.|Department of Immunology & Pathology, Monash University, Melbourne, VIC 3004, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: David Cs
authors.initials: DC
authors.lastname: Huang
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cory
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Herold
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.|Department of Microbiology & Immunology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D018448:Models, Immunological; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics* / Q000276:immunology; D009928:Organ Specificity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C096816:BCL2-related protein A1; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579094:Mcl1 protein, mouse; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C052617:Bcl2 protein, mouse; C579720:venetoclax