The life and death of immune cell types

The role of BCL-2 anti-apoptotic molecules

Emma M. Carrington, David M. Tarlinton, Daniel H. Gray, Nicholas D. Huntington, Yifan Zhan, Andrew M. Lew

Research output: Contribution to journalReview ArticleOtherpeer-review

10 Citations (Scopus)

Abstract

Targeting survival mechanisms of immune cells may provide an avenue for immune intervention to dampen unwanted responses (e.g. autoimmunity, immunopathology and transplant rejection) or enhance beneficial ones (e.g. immune deficiency, microbial defence and cancer immunotherapy). The selective survival mechanisms of the various immune cell types also avails the possibility of specific tailoring of such interventions. Here, we review the role of the BCL-2 anti-apoptotic family members (BCL-2, BCL-XL, BCL-W, MCL-1 and A1) on cell death/survival of the major immune cell types, for example, T, NK, B, dendritic cell (DC) lineages. There is both selectivity and redundancy among this family. Selectivity comes partly from the expression levels in each of the cell types. For example, plasmacytoid DC express abundant BCL-2 and are susceptible to BCL-2 antagonism or deficiency, whereas conventional DC express abundant A1 and are susceptible to A1 deficiency. There is, however, also functional redundancy; for example, overexpression of MCL-1 can override BCL-2 antagonism in plasmacytoid DC. Moreover, susceptibility to another anti-apoptotic family member can be unmasked, when one or other member is removed. These dual principles of selectivity and redundancy should guide the use of antagonists for manipulating immune cells.

Original languageEnglish
Pages (from-to)870-877
Number of pages8
JournalImmunology and Cell Biology
Volume95
Issue number10
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

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abstract = "Targeting survival mechanisms of immune cells may provide an avenue for immune intervention to dampen unwanted responses (e.g. autoimmunity, immunopathology and transplant rejection) or enhance beneficial ones (e.g. immune deficiency, microbial defence and cancer immunotherapy). The selective survival mechanisms of the various immune cell types also avails the possibility of specific tailoring of such interventions. Here, we review the role of the BCL-2 anti-apoptotic family members (BCL-2, BCL-XL, BCL-W, MCL-1 and A1) on cell death/survival of the major immune cell types, for example, T, NK, B, dendritic cell (DC) lineages. There is both selectivity and redundancy among this family. Selectivity comes partly from the expression levels in each of the cell types. For example, plasmacytoid DC express abundant BCL-2 and are susceptible to BCL-2 antagonism or deficiency, whereas conventional DC express abundant A1 and are susceptible to A1 deficiency. There is, however, also functional redundancy; for example, overexpression of MCL-1 can override BCL-2 antagonism in plasmacytoid DC. Moreover, susceptibility to another anti-apoptotic family member can be unmasked, when one or other member is removed. These dual principles of selectivity and redundancy should guide the use of antagonists for manipulating immune cells.",
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The life and death of immune cell types : The role of BCL-2 anti-apoptotic molecules. / Carrington, Emma M.; Tarlinton, David M.; Gray, Daniel H.; Huntington, Nicholas D.; Zhan, Yifan; Lew, Andrew M.

In: Immunology and Cell Biology, Vol. 95, No. 10, 01.11.2017, p. 870-877.

Research output: Contribution to journalReview ArticleOtherpeer-review

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