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Publication

Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response.

Immunity | 2018

Natural killer (NK) cells are innate lymphocytes that display features of adaptive immunity during viral infection. Biallelic mutations in IRF8 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 remains unknown. Here, we show that cell-intrinsic IRF8 was required for NK-cell-mediated protection against mouse cytomegalovirus infection. During viral exposure, NK cells upregulated IRF8 through interleukin-12 (IL-12) signaling and the transcription factor STAT4, which promoted epigenetic remodeling of the Irf8 locus. Moreover, IRF8 facilitated the proliferative burst of virus-specific NK cells by promoting expression of cell-cycle genes and directly controlling Zbtb32, a master regulator of virus-driven NK cell proliferation. These findings identify the function and cell-type-specific regulation of IRF8 in NK-cell-mediated antiviral immunity and provide a mechanistic understanding of viral susceptibility in patients with IRF8 mutations.

Pubmed ID: 29858012 RIS Download

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Associated grants

Agency: NIAID NIH HHS, United States
Id: R01 AI100874
Agency: NCI NIH HHS, United States
Id: T32 CA009149
Agency: NCI NIH HHS, United States
Id: P30 CA008748
Agency: NIAID NIH HHS, United States
Id: F30 AI122721
Agency: NIGMS NIH HHS, United States
Id: T32 GM007739
Agency: NIAID NIH HHS, United States
Id: F30 AI136239
Agency: NIAID NIH HHS, United States
Id: R01 AI130043

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R Project for Statistical Computing (tool)

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Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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RRID:SCR_006646

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