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STAT4 promotes Bhlhe40 induction to drive protective IFN-g from natural killer cells during viral infection [STAT4 CUT&RUN]

UID: 10949

Author(s): Kim, Hyunu*, Sun, Joseph C.* * MSK affiliated

Description
Summary from GEO:

"NK cells represent a cellular component of the mammalian innate immune system, and mount rapid responses against viral infection, including the secretion of the potent anti-viral effector cytokine IFN-g. Following mouse cytomegalovirus (MCMV) infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-g production during MCMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-g by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-g secretion by NK cells during viral infection."

Overall design from GEO:

"To investigate the binding sites of STAT4 in NK cells during homeostasis and 3 hour IL-12 + IL-18 cytokine stimulation, we performed STAT4 CUT&RUN using WT and STAT4-/-(STAT4KO) mice.
All cells for each conditions were sorted and cultured in complete IMDM + IL-15 media for 5 days prior. These cells were then washed and incubated in complete IMDM media without IL-15 for 1 hour prior to addition of appropriate stimulus, unstimulated or 3 hour IL-12 + IL-18. After stimulation, these CD49b+ NK cells were FACS sorted and CUT&RUN was performed, where replicates are biologically paired across stimulation conditions."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE242911

Access via BioProject


Accession #: PRJNA1015269

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provide open access to these files.
Associated Publications
Equipment Used
Illumina NovaSeq 6000
Dataset Format(s)
TSV, TAR, BW
Dataset Size
259 KB (TSV), 2.2 GB (TAR)
Data Catalog Record Updated
2023-10-17