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

Mice, Knockout Recombination, Genetic 0303 health sciences Thymocytes Receptors, Notch Cell Survival Receptors, Antigen, T-Cell, alpha-beta Article Histone Deacetylases Repressor Proteins Mice 03 medical and health sciences Organ Specificity Animals Natural Killer T-Cells Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor Gene Deletion
DOI: 10.1038/ncomms2580 Publication Date: 2013-03-12T09:41:55Z
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.
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