RRC ID 48892
Author Yanagihara T, Tomino T, Uruno T, Fukui Y.
Title Thymic epithelial cell-specific deletion of Jmjd6 reduces Aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes.
Journal 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.
Volume 489(1)
Pages 8-13
Published 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
Times Cited 2
Mice RBRC01834