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Epigenetic modifications induced by Blimp-1 Regulate CD8⁺ T cell memory progression during acute virus infection.

Abstract：

:The transcription factor Blimp-1 regulates the overall accumulation of virus-specific CD8⁺ T cells during acute viral infections. We found that increased proliferation and survival of Blimp-1-deficient CD8⁺ T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8⁺ T cell response. Genome-wide chromatin immunoprecipitation (ChIP) sequencing analysis identified Il2ra and Cd27 as direct targets of Blimp-1. At the peak of the antiviral response, but not earlier, Blimp-1 recruited the histone-modifying enzymes G9a and HDAC2 to the Il2ra and Cd27 loci, thereby repressing expression of these genes. In the absence of Blimp-1, Il2ra and Cd27 exhibited enhanced histone H3 acetylation and reduced histone H3K9 trimethylation. These data elucidate a central mechanism by which Blimp-1 acts as an epigenetic regulator and enhances the numbers of short-lived effector cells while suppressing the development of memory-precursor CD8⁺ T cells.

journal_name

Immunity

journal_title

Immunity

authors

Shin HM,Kapoor V,Guan T,Kaech SM,Welsh RM,Berg LJ

doi

10.1016/j.immuni.2013.08.032

subject

Has Abstract

pub_date

2013-10-17 00:00:00

pages

661-75

issue

4

eissn

1074-7613

issn

1097-4180

journal_volume

39

pub_type

杂志文章

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