Journal
CELL DEATH AND DIFFERENTIATION
Volume 24, Issue 5, Pages 878-888Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2017.30
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Funding
- Rebecca L. Cooper Foundation
- National Health and Medical Research Council of Australia (NHMRC) [1037321, 1043414, 1080321, 1105209, 461221, 1042629, 1020363, 1016701, 1054925, 1060675, 1016647, 1049720]
- Leukemia and Lymphoma Society (LLS) Specialized Center of Research grant [7001-13]
- Cancer Council Victoria (CCV) [1102104]
- Austrian Academy of Science (OAW)
- Leukemia Foundation National Research Program PhD Scholarship
- NHMRC Independent Research Institutes Infrastructure Support Scheme grant [361646]
- Victorian State Government
- National Health and Medical Research Council of Australia [1060675] Funding Source: NHMRC
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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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