Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

Sathe, Priyanka, Delconte, Rebecca B., Souza-Fonseca-Guimaraes, Fernando, Seillet, Cyril, Chopin, Michael, Vandenberg, Cassandra J., Rankin, Lucille C., Mielke, Lisa A., Vikstrom, Ingela, Kolesnik, Tatiana B., Nicholson, Sandra E., Vivier, Eric, Smyth, Mark J., Nutt, Stephen L., Glaser, Stefan P., Strasser, Andreas, Belz, Gabrielle T., Carotta, Sebastian and Huntington, Nicholas D. (2014) Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nature Communications, 5 1-10. doi:10.1038/ncomms5539

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Author Sathe, Priyanka
Delconte, Rebecca B.
Souza-Fonseca-Guimaraes, Fernando
Seillet, Cyril
Chopin, Michael
Vandenberg, Cassandra J.
Rankin, Lucille C.
Mielke, Lisa A.
Vikstrom, Ingela
Kolesnik, Tatiana B.
Nicholson, Sandra E.
Vivier, Eric
Smyth, Mark J.
Nutt, Stephen L.
Glaser, Stefan P.
Strasser, Andreas
Belz, Gabrielle T.
Carotta, Sebastian
Huntington, Nicholas D.
Title Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells
Formatted title
Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-08-14
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ncomms5539
Open Access Status File (Publisher version)
Volume 5
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
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