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 journalArticle

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

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Natural Killer T-Cells
T-cells
cells
T-Lymphocytes
Cell Lineage
T-Cell Antigen Receptor
knockout mice
Transgenes
Knockout Mice
deletion
proteins
Proteins
causes

ASJC Scopus subject areas

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

Cite this

Thapa, P., Das, J., McWilliams, D., Shapiro, M., Sundsbak, R., Nelson-Holte, M., ... Shapiro, V. S. (2013). The transcriptional repressor NKAP is required for the development of iNKT cells. Nature Communications, 4, [1582]. https://doi.org/10.1038/ncomms2580

The transcriptional repressor NKAP is required for the development of iNKT cells. / Thapa, Puspa; Das, Joy; McWilliams, Douglas; Shapiro, Michael; Sundsbak, Rhianna; Nelson-Holte, Molly; Tangen, Sarah; Anderson, Joshua; Desiderio, Stephen; Hiebert, Scott; Sant'Angelo, Derek B.; Shapiro, Virginia Smith.

In: Nature Communications, Vol. 4, 1582, 2013.

Research output: Contribution to journalArticle

Thapa, P, Das, J, McWilliams, D, Shapiro, M, Sundsbak, R, Nelson-Holte, M, Tangen, S, Anderson, J, Desiderio, S, Hiebert, S, Sant'Angelo, DB & Shapiro, VS 2013, 'The transcriptional repressor NKAP is required for the development of iNKT cells', Nature Communications, vol. 4, 1582. https://doi.org/10.1038/ncomms2580
Thapa P, Das J, McWilliams D, Shapiro M, Sundsbak R, Nelson-Holte M et al. The transcriptional repressor NKAP is required for the development of iNKT cells. Nature Communications. 2013;4. 1582. https://doi.org/10.1038/ncomms2580
Thapa, Puspa ; Das, Joy ; McWilliams, Douglas ; Shapiro, Michael ; Sundsbak, Rhianna ; Nelson-Holte, Molly ; Tangen, Sarah ; Anderson, Joshua ; Desiderio, Stephen ; Hiebert, Scott ; Sant'Angelo, Derek B. ; Shapiro, Virginia Smith. / The transcriptional repressor NKAP is required for the development of iNKT cells. In: Nature Communications. 2013 ; Vol. 4.
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