The IL-15–AKT–XBP1s signaling pathway contributes to effector functions and survival in human NK cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12-10

AUTHORS

Yufeng Wang, Yibo Zhang, Ping Yi, Wenjuan Dong, Ansel P. Nalin, Jianying Zhang, Zheng Zhu, Lichao Chen, Don M. Benson, Bethany L. Mundy-Bosse, Aharon G. Freud, Michael A. Caligiuri, Jianhua Yu

ABSTRACT

Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells1. Here we identified a signaling pathway—involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes2,3—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. More... »

PAGES

10-17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41590-018-0265-1

DOI

http://dx.doi.org/10.1038/s41590-018-0265-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110288631

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30538328


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33 schema:description Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells1. Here we identified a signaling pathway—involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes2,3—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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