The IL-15-AKT-XBP1s signaling pathway contributes to effector functions and survival in human NK cells.

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 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-apop

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6293989 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature