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

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2013