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

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

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24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)878-888
Number of pages11
JournalCell Death and Differentiation
Volume24
Issue number5
DOIs
Publication statusPublished - 1 May 2017

Cite this

Carrington, E. M., Zhan, Y., Brady, J. L., Zhang, J. G., Sutherland, R. M., Anstee, N. S., Schenk, R. L., Vikstrom, I. B., Delconte, R. B., Segal, D., Huntington, N. D., Bouillet, P., Tarlinton, D. M., Huang, D. C. S., Strasser, A., Cory, S., Herold, M. J., & Lew, A. M. (2017). Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo. Cell Death and Differentiation, 24(5), 878-888. https://doi.org/10.1038/cdd.2017.30