論文 - 詳細
| RRC ID | 48892 |
|---|---|
| 著者 | Yanagihara T, Tomino T, Uruno T, Fukui Y. |
| タイトル | Thymic epithelial cell-specific deletion of Jmjd6 reduces Aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity. Here we report that TEC-specific deletion of Jmjd6 exacerbates development of autoimmune diabetes in a mouse model, which express both ovalbumin (OVA) under the control of the rat insulin gene promoter and OT-I T cell receptor specific for OVA peptide bound to major histocompatibility complex class I Kb molecules. We found that Aire protein expression in mTECs was reduced in the absence of Jmjd6, with retention of intron 2 in Aire transcripts. Our results thus demonstrate the importance of Jmjd6 in establishment of immunological tolerance in a more physiological setting. |
| 巻・号 | 489(1) |
| ページ | 8-13 |
| 公開日 | 2017-7-15 |
| DOI | 10.1016/j.bbrc.2017.05.113 |
| PII | S0006-291X(17)30997-X |
| PMID | 28546003 |
| MeSH | Animals Diabetes Mellitus, Type 1 / metabolism* Diabetes Mellitus, Type 1 / pathology Disease Models, Animal* Epithelial Cells / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Receptors, Cell Surface / deficiency* Receptors, Cell Surface / metabolism* Thymus Gland / metabolism* Thymus Gland / pathology Transcription Factors / genetics* Transcription Factors / metabolism |
| IF | 2.985 |
| 引用数 | 2 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC01834 |