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

doi:10.1038/ncomms2580

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

Immunology

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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 language	English (US)
Article number	1582
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2580
State	Published - 2013

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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@article{7d1bc4bd1daf4319be4d138eef7e1e8e,

title = "The transcriptional repressor NKAP is required for the development of iNKT cells",

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.",

author = "Puspa Thapa and Joy Das and Douglas McWilliams and Michael Shapiro and Rhianna Sundsbak and Molly Nelson-Holte and Sarah Tangen and Joshua Anderson and Stephen Desiderio and Scott Hiebert and Sant'Angelo, {Derek B.} and Shapiro, {Virginia Smith}",

note = "Funding Information: We thank Dr Tasuku Honjo for the floxed RBP-Jk mice, and Dr Al Singer for the Bcl-2 transgenic mice. We thank the National Institutes of Health (NIH) Tetramer Facility for the PE-labelled PBS-57/CD1d and PE-labelled empty CD1d tetramers. This work was supported by NIH grant R21 AI093944 to V.S.S., and D.B.S. and J.D. were supported by NIH NIAID R01 AI083988 and AI059739, and by the Robert Wood Johnson Foundation (grant number 67038) to the Child Health Institute.",

year = "2013",

doi = "10.1038/ncomms2580",

language = "English (US)",

volume = "4",

journal = "Nature communications",

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AU - Thapa, Puspa

AU - Das, Joy

AU - McWilliams, Douglas

AU - Shapiro, Michael

AU - Sundsbak, Rhianna

AU - Nelson-Holte, Molly

AU - Tangen, Sarah

AU - Anderson, Joshua

AU - Desiderio, Stephen

AU - Hiebert, Scott

AU - Sant'Angelo, Derek B.

AU - Shapiro, Virginia Smith

N1 - Funding Information: We thank Dr Tasuku Honjo for the floxed RBP-Jk mice, and Dr Al Singer for the Bcl-2 transgenic mice. We thank the National Institutes of Health (NIH) Tetramer Facility for the PE-labelled PBS-57/CD1d and PE-labelled empty CD1d tetramers. This work was supported by NIH grant R21 AI093944 to V.S.S., and D.B.S. and J.D. were supported by NIH NIAID R01 AI083988 and AI059739, and by the Robert Wood Johnson Foundation (grant number 67038) to the Child Health Institute.

PY - 2013

Y1 - 2013

N2 - 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.

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

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