| First Author | Yue X | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 41 | Pages | 17105-10 |
| PubMed ID | 21949387 | Mgi Jnum | J:177469 |
| Mgi Id | MGI:5295138 | Doi | 10.1073/pnas.1109095108 |
| Citation | Yue X, et al. (2011) Essential role of Mediator subunit Med1 in invariant natural killer T-cell development. Proc Natl Acad Sci U S A 108(41):17105-10 |
| abstractText | 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 alphabeta 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 Valpha14-Jalpha18 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-2Rbeta and T-bet expression and could not complete terminal maturation. Thus, Med1 is essential for a complete intrathymic development of iNKT cells. |
