Essential role of Mediator subunit Med1 in invariant natural killer T-cell development.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 108 (2011-10-11), Heft 41, S. 17105-17110
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Essential role of Mediator subunit Med1 in invariant natural killer T-cell development.
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Autor/in / Beteiligte Person: | Yue, Xiaojing ; Izcue, Ana ; Borggrefe, Tilman |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 108 (2011-10-11), Heft 41, S. 17105-17110 |
Veröffentlichung: | 2011 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.1109095108 |
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