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.
authors.affiliation: Department of Immunology, Mayo Clinic, 4-14 Guggenheim Building, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Puspa
authors.initials: P
authors.lastname: Thapa
authors.forename: Joy
authors.initials: J
authors.lastname: Das
authors.forename: Douglas
authors.initials: D
authors.lastname: McWilliams
authors.forename: Michael
authors.initials: M
authors.lastname: Shapiro
authors.forename: Rhianna
authors.initials: R
authors.lastname: Sundsbak
authors.forename: Molly
authors.initials: M
authors.lastname: Nelson-Holte
authors.forename: Sarah
authors.initials: S
authors.lastname: Tangen
authors.forename: Joshua
authors.initials: J
authors.lastname: Anderson
authors.forename: Stephen
authors.initials: S
authors.lastname: Desiderio
authors.forename: Scott
authors.initials: S
authors.lastname: Hiebert
authors.forename: Derek B
authors.initials: DB
authors.lastname: Sant'angelo
authors.forename: Virginia Smith
authors.initials: VS
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D002470:Cell Survival; D017353:Gene Deletion; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006655:Histone Deacetylases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C560431:NKAP protein, mouse