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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • NKAP protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Notch
  • Repressor Proteins
  • Histone Deacetylases
  • histone deacetylase 3