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Transcription factor IRF8 orchestrates the adaptive natural killer cell response

UID: 10378

Author(s): Lau, Colleen M.*, Sun, Joseph C.* * MSK affiliated

Publisher(s): Memorial Sloan Kettering Cancer Center

Description
RNA-seq performed on NK cells harvested during in-vivo infection.

Natural killer (NK) cells are innate lymphocytes that have been recently appreciated to display features of adaptive immunity in response to viral infection. Biallelic mutations in the IRF8 gene have been reported to cause familial NK cell deficiency and susceptibility to severe viral infection in humans; however, the precise role of this transcription factor in regulating NK cell function remained unknown. Here, we show that IRF8 is required in a cell-intrinsic manner for NK cell-mediated protection against mouse cytomegalovirus (MCMV) infection. During exposure to MCMV, IRF8 is robustly upregulated in NK cells by IL-12 and STAT4, which promotes epigenetic remodeling of the Irf8 locus. Moreover, IRF8 facilitates the proliferative burst of virus-specific NK cells by promoting expression of a suite of DNA replication and cell cycle genes, and directly regulating Zbtb32, a master regulator of NK cell proliferation during viral challenge. These results identify a novel function and cell-type specific regulation for IRF8 in host antiviral immunity, and provide a mechanistic understanding of virus susceptibility in patients with IRF8 mutations.
Subject of Study
Subject(s)
Access via GEO

RNA-seq of NK cells
Accession #: GSE112948

Access Restrictions
Free to All
Access Instructions
Available for download as tar SRA file from NCBI's Gene Expression Omnibus.
Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2500
Dataset Format(s)
SRA, TAR
Dataset Size
1.1 MB
Data Catalog Record Updated
2021-10-26