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

被引：88

作者：

Wang, Yufeng ^{[1
,2
]}

Zhang, Yibo ^{[1
]}

Yi, Ping ^{[1
,3
]}

Dong, Wenjuan ^{[1
,4
]}

Nalin, Ansel P. ^{[1
,5
]}

Zhang, Jianying ^{[6
]}

Zhu, Zheng ^{[1
,4
]}

Chen, Lichao ^{[1
]}

Benson, Don M. ^{[1
,2
]}

Mundy-Bosse, Bethany L. ^{[1
,2
]}

Freud, Aharon G. ^{[1
,7
]}

Caligiuri, Michael A. ^{[4
,8
]}

Yu, Jianhua ^{[1
,2
,4
,8
]}

机构：

[1] Ohio State Univ, Comprehens Canc Ctr, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA

[3] Third Mil Med Univ, Affiliated Hosp 3, Chongqing, Peoples R China

[4] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, 1500 E Duarte Rd, Duarte, CA 91010 USA

[5] Ohio State Univ, Med Scientist Training Program, Columbus, OH 43210 USA

[6] City Hope Natl Med Ctr, Dept Informat Sci, Div Biostat, 1500 E Duarte Rd, Duarte, CA 91010 USA

[7] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA

[8] City Hope Natl Med Ctr, Hematol Malignancies & Stem Cell Transplantat Ins, 1500 E Duarte Rd, Duarte, CA 91010 USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ENDOPLASMIC-RETICULUM STRESS; NATURAL-KILLER-CELLS; TERMINAL MATURATION; PROTEIN-SYNTHESIS; XBP1; INTERLEUKIN-15; P110-DELTA; EXPRESSION; REGULATOR; DIFFERENTIATION;

D O I：

10.1038/s41590-018-0265-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：10 / +

页数：9

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