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
|
リソース情報 |
実験動物マウス |
RBRC01834 |