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

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 Shapiro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1582
JournalNature communications
Volume4
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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