Critical functions for STAT5 tetramers in the maturation and survival of natural killer cells

Nature Communications
Jian-Xin LinWarren J Leonard

Abstract

Interleukin-15 (IL-15) is essential for the development and maintenance of natural killer (NK) cells. IL-15 activates STAT5 proteins, which can form dimers or tetramers. We previously found that NK cell numbers are decreased in Stat5a-Stat5b tetramer-deficient double knockin (DKI) mice, but the mechanism was not investigated. Here we show that STAT5 dimers are sufficient for NK cell development, whereas STAT5 tetramers mediate NK cell maturation and the expression of maturation-associated genes. Unlike the defective proliferation of Stat5 DKI CD8+ T cells, Stat5 DKI NK cells have normal proliferation to IL-15 but are susceptible to death upon cytokine withdrawal, with lower Bcl2 and increased active caspases. These findings underscore the importance of STAT5 tetramers in maintaining NK cell homoeostasis. Moreover, defective STAT5 tetramer formation could represent a cause of NK cell immunodeficiency, and interrupting STAT5 tetramer formation might serve to control NK leukaemia.

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Citations

Mar 27, 2018·Immunology and Cell Biology·Jai RautelaNicholas D Huntington
Nov 20, 2018·Immunology·Marc Brillantes, Aimee M Beaulieu
Jan 17, 2019·Annual Review of Immunology·Jian-Xin Lin, Warren J Leonard
Mar 13, 2020·Frontiers in Immunology·Nuriban Valero-Pacheco, Aimee M Beaulieu
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Dec 11, 2019·Cancers·Anna OrlovaRichard Moriggl
Aug 28, 2020·Frontiers in Immunology·Jiacheng Bi, Xuefu Wang
Dec 14, 2018·Frontiers in Immunology·Peng Li, Warren J Leonard
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Datasets Mentioned

BETA
GM-CSF
GSE101470
GSE36890

Methods Mentioned

BETA
RNA-Seq
flow cytometry
ChIP-Seq
Assay
PCR
ChIP

Software Mentioned

MACS
FlowJo
Prism
Gene Set Enrichment Analysis algorithm ( GSEA
UCSC browser
R
seqMiner
TopHat
pheatmap
DataGraph

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