| First Author | Yanagihara T | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 489 |
| Issue | 1 | Pages | 8-13 |
| PubMed ID | 28546003 | Mgi Jnum | J:251421 |
| Mgi Id | MGI:6103294 | Doi | 10.1016/j.bbrc.2017.05.113 |
| Citation | Yanagihara T, et al. (2017) Thymic epithelial cell-specific deletion of Jmjd6 reduces Aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes. Biochem Biophys Res Commun 489(1):8-13 |
| abstractText | 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 K(b) 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. |
