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An XBP1s-PIM-2 positive feedback loop controls IL-15-mediated survival of natural killer cells.
Ma, Shoubao; Han, Jingjing; Li, Zhenlong; Xiao, Sai; Zhang, Jianying; Yan, Jiazhuo; Tang, Tingting; Barr, Tasha; Kraft, Andrew S; Caligiuri, Michael A; Yu, Jianhua.
Affiliation
  • Ma S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Han J; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Li Z; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Xiao S; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Zhang J; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Yan J; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Tang T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Barr T; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Kraft AS; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Caligiuri MA; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Yu J; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
Sci Immunol ; 8(81): eabn7993, 2023 03 17.
Article in En | MEDLINE | ID: mdl-36897958
ABSTRACT
Spliced X-box-binding protein 1 (XBP1s) is an essential transcription factor downstream of interleukin-15 (IL-15) and AKT signaling, which controls cell survival and effector functions of human natural killer (NK) cells. However, the precise mechanisms, especially the downstream targets of XBP1s, remain unknown. In this study, by using XBP1 conditional knockout mice, we found that XBP1s is critical for IL-15-mediated NK cell survival but not proliferation in vitro and in vivo. Mechanistically, XBP1s regulates homeostatic NK cell survival by targeting PIM-2, a critical anti-apoptotic gene, which in turn stabilizes XBP1s protein by phosphorylating it at Thr58. In addition, XBP1s enhances the effector functions and antitumor immunity of NK cells by recruiting T-bet to the promoter region of Ifng. Collectively, our findings identify a previously unknown mechanism by which IL-15-XBP1s signaling regulates the survival and effector functions of NK cells.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Serine-Threonine Kinases / Interleukin-15 / X-Box Binding Protein 1 Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Sci Immunol Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Serine-Threonine Kinases / Interleukin-15 / X-Box Binding Protein 1 Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Sci Immunol Year: 2023 Document type: Article