Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Elife. 2018 May 31;7. pii: e33057. doi: 10.7554/eLife.33057.

ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity.

Author information

1
Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
2
New York Genome Center, New York, United States.
3
Howard Hughes Medical Institute, Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, United States.

Abstract

Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less clear. We used HITS-CLIP to define ZFP36 targets in mouse T cells, revealing unanticipated actions in regulating T-cell activation, proliferation, and effector functions. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target abundance and translation, notably through novel AU-rich sites in coding sequence. Functional studies revealed that ZFP36 regulates early T-cell activation kinetics cell autonomously, by attenuating activation marker expression, limiting T cell expansion, and promoting apoptosis. Strikingly, loss of ZFP36 in vivo accelerated T cell responses to acute viral infection and enhanced anti-viral immunity. These findings uncover a critical role for ZFP36 RBPs in restraining T cell expansion and effector functions, and suggest ZFP36 inhibition as a strategy to enhance immune-based therapies.

KEYWORDS:

HITS-CLIP; RNA binding protein; T cell; anti-viral immunity; chromosomes; gene expression; immunology; inflammation; mouse; translation

PMID:
29848443
PMCID:
PMC6033538
DOI:
10.7554/eLife.33057
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center