Aire-dependent peripheral tissue antigen mRNAs in mTEC cells feature networking refractoriness to microRNA interaction

Immunobiology. 2015 Jan;220(1):93-102. doi: 10.1016/j.imbio.2014.08.015. Epub 2014 Aug 27.

Abstract

The downregulation of PTA genes in mTECs is associated with the loss of self-tolerance, and the role of miRNAs in this process is not fully understood. Therefore, we studied the expression of mRNAs and miRNAs in mTECs from autoimmune NOD mice during the period when loss of self-tolerance occurs in parallel with non-autoimmune BALB/c mice. Although the expression of the transcriptional regulator Aire was unchanged, we observed downregulation of a set of PTA mRNAs. A set of miRNAs was also differentially expressed in these mice. The reconstruction of miRNA-mRNA interaction networks identified the controller miRNAs and predicted the PTA mRNA targets. Interestingly, the known Aire-dependent PTAs exhibited pronounced refractoriness in the networking interaction with miRNAs. This study reveals the existence of a new mechanism in mTECs, and this mechanism may have importance in the control of self-tolerance.

Keywords: Aire gene; Peripheral tissue antigen; Post-transcriptional control; Self-tolerance; Thymus; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Animals
  • Animals, Newborn
  • Antigens / genetics*
  • Antigens / immunology
  • Cluster Analysis
  • Epistasis, Genetic*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Messenger / genetics*
  • Self Tolerance
  • Thymus Gland / cytology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Antigens
  • MicroRNAs
  • RNA, Messenger
  • Transcription Factors