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Nat Commun. 2013;4:1582. doi: 10.1038/ncomms2580.

The transcriptional repressor NKAP is required for the development of iNKT cells.

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1
Department of Immunology, Mayo Clinic, 4-14 Guggenheim Building, 200 First Street SW, Rochester, Minnesota 55905, USA.

Abstract

Invariant natural killer T cells have a distinct developmental pathway from conventional αβ T cells. Here we demonstrate that the transcriptional repressor NKAP is required for invariant natural killer T cell but not conventional T cell development. In CD4-cre NKAP conditional knockout mice, invariant natural killer T cell development is blocked at the double-positive stage. This cell-intrinsic block is not due to decreased survival or failure to rearrange the invariant Vα14-Jα18 T cell receptor-α chain, but is rescued by overexpression of a rec-Vα14-Jα18 transgene at the double-positive stage, thus defining a role for NKAP in selection into the invariant natural killer T cell lineage. Importantly, deletion of the NKAP-associated protein histone deacetylase 3 causes a similar block in the invariant natural killer T cell development, indicating that NKAP and histone deacetylase 3 functionally interact to control invariant natural killer T cell development.

PMID:
23481390
PMCID:
PMC3615467
DOI:
10.1038/ncomms2580
[Indexed for MEDLINE]
Free PMC Article
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