Search Tips

The IRE1-XBP1 pathway promotes natural killer cell responses against viral infection and cancer by regulation of c-Myc

UID: 11045

Author(s): Dong, Han, Adams, Nicholas M.*, Xu, Yichi*, Cao, Jin, Allan, David S.J., Carlyle, James R., Chen, Xi, Sun, Joseph C.*, Glimcher, Laurie H. * MSK affiliated

Description
Summary from GEO:

"Natural killer (NK) cells are critical mediators of host immunity against infectious disease and cancer. The intrinsic regulators of NK cells are not fully understood. Here, we demonstrate that the ER stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) critically drive NK cell-mediated responses against viral infection and tumors. IRE1α and XBP1 were essential for the robust expansion of activated mouse and human NK cells. Transcriptome analysis revealed the transcription factor c-Myc as a novel and direct target of XBP1 for downstream regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, whereas overexpression of XBP1 resulted in c-Myc hyperactivation. NK cells lacking c-Myc demonstrated a functional deficit comparable to IRE1α or XBP1 deficiency. Overall, our study identifies a novel IRE1-XBP1-cMyc axis in NK cell immunity, providing new insight into the host immune response against infection and cancer."

Overall design from GEO:

"Transcriptome analysis of activated and quiescent NK cells (WT and IRE1 KO)."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE113214

Access via BioProject


Accession #: PRJNA450435

Access via SRA


Accession #: SRP140561

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus. BioProject, and SRA databases provide open access to these files.
Associated Publications
Equipment Used
Illumina HiSeq 4000
Dataset Format(s)
TAR, TXT
Dataset Size
1.6 MB
Data Catalog Record Updated
2023-11-15