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

Thapa P, Das J, McWilliams D, Shapiro M, Sundsbak R, Nelson-Holte M, Tangen S, Anderson J, Desiderio S, Hiebert S, Sant'angelo DB, Shapiro VS
Nat Commun. 2013 4: 1582

PMID: 23481390 · PMCID: PMC3615467 · DOI:10.1038/ncomms2580

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.

MeSH Terms (14)

Animals Cell Survival Gene Deletion Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor Histone Deacetylases Mice Mice, Knockout Natural Killer T-Cells Organ Specificity Receptors, Antigen, T-Cell, alpha-beta Receptors, Notch Recombination, Genetic Repressor Proteins Thymocytes

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