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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Izcue, Ana Yue, Xiaojing Borggrefe, Tilman |
| Description | Author Affiliation: Yue X ( The Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany.); |
| 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 ß 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 V 14-J 18 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-2Rß and T-bet expression and could not complete terminal maturation. Thus, Med1 is essential for a complete intrathymic development of iNKT cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 41 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Mediator Complex Subunit 1 Immunology Natural Killer T-Cells Metabolism Animals Cell Differentiation Cell Lineage Genetics Gene Expression Interleukin-2 Receptor Beta Subunit Deficiency Mice Mice, Knockout Mice, Transgenic Cytology Receptors, Antigen, T-Cell, Alpha-beta T-Box Domain Proteins T-Lymphocyte Subsets Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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