Cutting Edge: STAT1-Mediated Epigenetic Control of Rsad2 Promotes Clonal Expansion of Antiviral NK Cells

Autor:	Colleen M. Lau, Clair D. Geary, Gabriela M. Wiedemann, Joseph C. Sun
Rok vydání:	2020
Předmět:	Innate immune system Immunology Biology Acquired immune system Chromatin Cell biology 03 medical and health sciences 0302 clinical medicine Immunity Cell culture Viperin Immunology and Allergy H3K4me3 Epigenetics 030215 immunology
Zdroj:	The Journal of Immunology. 205:21-25
ISSN:	1550-6606 0022-1767
DOI:	10.4049/jimmunol.2000086
Popis:	NK cells represent a cellular component of innate immunity but possess features of adaptive immunity, including clonal expansion and establishment of long-lived memory following infection. During mouse CMV (MCMV) infection, we observed Rsad2 (which encodes Viperin) to be among the most highly induced IFN stimulatory genes in activated NK cells, correlating with increased chromatin accessibility at the Rsad2 gene locus. Furthermore, in NK cells stimulated with IFN-α, the promoter region of Rsad2 was enriched for STAT1 binding and the permissive histone mark H3K4me3. IFN-αR– and STAT1-deficient NK cells showed an impairment of Rsad2 induction and chromatin accessibility during MCMV infection. Finally, Rsad2-deficient NK cells were defective in clonal expansion and memory formation following exposure to MCMV, in part because of greater apoptosis. Thus, our study reveals a critical mechanism of STAT1-mediated epigenetic control of Rsad2 to promote the adaptive behavior of NK cells during viral infection.
Databáze:	OpenAIRE
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