کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5505400 | 1400268 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Thymic epithelial cell-specific deletion of Jmjd6 reduces Aire protein expression.
- Thymic epithelial cell-specific deletion of Jmjd6 exacerbates autoimmune diabetes.
- Aire expression is reduced in the absence of Jmjd6, through intron 2 retention.
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.
Journal: Biochemical and Biophysical Research Communications - Volume 489, Issue 1, 15 July 2017, Pages 8-13