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

• DOI: 10.1038/ncomms2580
• Publication Date: 2013-03-12T09:41:55Z
• Authors: Puspa Thapa; Joy Das; Douglas McWilliams; Michael Shapiro; Rhianna Sundsbak; Molly Nelson-Holte; Sarah Tangen; Joshua Anderson; Stephen Desiderio; Scott Hiebert; Derek B. Sant’Angelo; Virginia Smith Sh...
• Keywords: Mice, Knockout; Recombination, Genetic; 0301 basic medicine; 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

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.