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Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo

by Strasser, Andreas , Huang, David CS , Lew, Andrew M , Zhan, Yifan , Bouillet, Philippe , Tarlinton, David M , Segal, David , Brady, Jamie L , Huntington, Nicholas D , Herold, Marco J , Carrington, Emma M , Cory, Suzanne , Vikstrom, Ingela B , Anstee, Natasha S , Sutherland, Robyn M , Delconte, Rebecca B , Schenk, Robyn L , Zhang, Jian-Guo

in 13/31 / 631/250/1619 / 631/250/1932 / 64 / 64/60 / Animals / Antineoplastic Agents - pharmacology / Apoptosis / B-Lymphocytes - cytology / B-Lymphocytes - drug effects / B-Lymphocytes - immunology / Biochemistry / Biomedical and Life Sciences / Bridged Bicyclo Compounds, Heterocyclic - pharmacology / CD4-Positive T-Lymphocytes - cytology / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - cytology / CD8-Positive T-Lymphocytes - drug effects / CD8-Positive T-Lymphocytes - immunology / Cell Biology / Cell Cycle Analysis / Cell death / Cell Survival / Cytochrome / Dendritic cells / Dendritic Cells - cytology / Dendritic Cells - drug effects / Dendritic Cells - immunology / FDA approval / Flow Cytometry / Gene Expression Regulation - immunology / Immunity, Innate / Immunology / Immunophenotyping / Life Sciences / Lymphocytes / Medical research / Mice / Mice, Inbred C57BL / Mice, Transgenic / Minor Histocompatibility Antigens - genetics / Minor Histocompatibility Antigens - immunology / Models, Immunological / Myeloid Cell Leukemia Sequence 1 Protein - genetics / Myeloid Cell Leukemia Sequence 1 Protein - immunology / Organ Specificity / Original Paper / Proteins / Proto-Oncogene Proteins c-bcl-2 - genetics / Proto-Oncogene Proteins c-bcl-2 - immunology / Signal Transduction / Stem Cells / Sulfonamides - pharmacology

2017

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Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo

2017

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Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo

2017

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Journal Article

Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo

Strasser, Andreas,

Huang, David CS,

Lew, Andrew M,

Zhan, Yifan,

Bouillet, Philippe,

Tarlinton, David M,

Segal, David,

Brady, Jamie L,

Huntington, Nicholas D,

Herold, Marco J,

Carrington, Emma M,

Cory, Suzanne,

Vikstrom, Ingela B,

Anstee, Natasha S,

Sutherland, Robyn M,

Delconte, Rebecca B,

Schenk, Robyn L,

Zhang, Jian-Guo

2017

Overview

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.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

13/31

/ 631/250/1619

/ 631/250/1932

/ 64

/ 64/60

/ Animals

/ Antineoplastic Agents - pharmacology