Unknown

Dataset Information

0

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 ?? 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-2R? and T-bet expression and could not complete terminal maturation. Thus, Med1 is essential for a complete intrathymic development of iNKT cells.

SUBMITTER: Yue X 

PROVIDER: S-EPMC3193226 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

altmetric image

Publications

Essential role of Mediator subunit Med1 in invariant natural killer T-cell development.

Yue Xiaojing X   Izcue Ana A   Borggrefe Tilman T  

Proceedings of the National Academy of Sciences of the United States of America 20110926 41


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 bu  ...[more]

Similar Datasets

| S-EPMC8020658 | biostudies-literature
2021-03-12 | GSE157283 | GEO
| S-EPMC5672022 | biostudies-literature
| S-EPMC6743333 | biostudies-literature
| S-EPMC4284579 | biostudies-literature
| S-EPMC7018522 | biostudies-literature
2017-10-15 | GSE104205 | GEO
| S-EPMC3869389 | biostudies-literature
| S-EPMC2560993 | biostudies-literature
| S-EPMC5787561 | biostudies-literature