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

P Thapa, J Das, D McWilliams, M Shapiro… - Nature …, 2013 - nature.com
P Thapa, J Das, D McWilliams, M Shapiro, R Sundsbak, M Nelson-Holte, S Tangen…
Nature communications, 2013nature.com
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 …
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.
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