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

Author

Listed:
  • Puspa Thapa

    (Mayo Clinic)

  • Joy Das

    (Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School)

  • Douglas McWilliams

    (Mayo Clinic)

  • Michael Shapiro

    (Mayo Clinic)

  • Rhianna Sundsbak

    (Mayo Clinic)

  • Molly Nelson-Holte

    (Mayo Clinic)

  • Sarah Tangen

    (Mayo Clinic)

  • Joshua Anderson

    (Mayo Clinic)

  • Stephen Desiderio

    (and Institute for Cell Engineering, The Johns Hopkins University School of Medicine)

  • Scott Hiebert

    (Vanderbilt University School of Medicine, 512 Preston Research Building, Nashville, Tennessee 37232, USA)

  • Derek B. Sant’Angelo

    (Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School)

  • Virginia Smith Shapiro

    (Mayo Clinic)

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.

Suggested Citation

  • 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 & Virgi, 2013. "The transcriptional repressor NKAP is required for the development of iNKT cells," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2580
    DOI: 10.1038/ncomms2580
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