title: Essential role of Mediator subunit Med1 in invariant natural killer T-cell development.
abstract: CD1d-restricted invariant NKT (iNKT) cells are a unique lineage of T lymphocytes that regulate both innate and adaptive immunity. The Mediator complex forms the bridge between transcriptional activators and the general transcription machinery. Med1/TRAP220 (also called DRIP205) is a key component of Mediator that interacts with ligand-bound hormone receptors, such as the vitamin D receptor. Here, we show that T-cell-specific Med1 deficiency results in a specific block in iNKT cell development but the development of conventional αβ T cells remains grossly normal. The defect is cell-intrinsic and depends neither on apoptosis, cell-cycle control, nor on CD1d expression of CD4(+)CD8(+) double-positive thymocytes. Surprisingly, ectopic expression of a Vα14-Jα18 T-cell receptor transgene completely rescues the defect caused by Med1 deficiency. At the molecular level, thymic iNKT cells in Med1(-/-) animals display reduced levels of IL-2Rβ and T-bet expression and could not complete terminal maturation. Thus, Med1 is essential for a complete intrathymic development of iNKT cells.
authors.affiliation: The Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg,  Germany.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yue
authors.forename: Ana
authors.initials: A
authors.lastname: Izcue
authors.forename: Tilman
authors.initials: T
authors.lastname: Borggrefe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D056913:Mediator Complex Subunit 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor