期刊
NATURE IMMUNOLOGY
卷 20, 期 1, 页码 10-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0265-1
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资金
- National Institutes of Health [AI129582, NS106170, CA185301, CA210087, CA068458]
- Leukemia and Lymphoma Society [6503-17, 1364-19]
- American Cancer Society [RSG-14-243-01-LIB]
- Gabrielle's Angel Cancer Research Foundation [87]
Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells(1). Here we identified a signaling pathway-involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes(2,3)-that was activated in response to IL-15 in human NK cells. IL-15 induced the phosphorylation of AKT, which led to the deubiquitination, increased stability and nuclear accumulation of XBP1s protein. XBP1s bound to and recruited the transcription factor T-BET to the gene encoding granzyme B, leading to increased transcription. XBP1s positively regulated the cytolytic activity of NK cells against leukemia cells and was also required for IL-15-mediated NK cell survival through an anti-apoptotic mechanism. Thus, the newly identified IL-15-AKT-XBP1s signaling pathway contributes to enhanced effector functions and survival of human NK cells.
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