P Thapa, J Das, D McWilliams, M Shapiro, R Sundsbak, M Nelson-Holte, S Tangen, J Anderson, S Desiderio, S Hiebert, DB Sant'angelo, VS Shapiro. (2013). "The transcriptional repressor NKAP is required for the development of iNKT cells." Nat Commun. 4, 1582. PMID: 23481390 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