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

Author(s)

Macedo, Claudia ^[1] ; Oliveira, Ernna H. ^[1] ; Almeida, Renata S. ^[1] ; Donate, Paula B. ^[1] ; Fornari, Thais A. ^[1] ; Pezzi, Nicole ^[1] ; Sakamoto-Hojo, Elza T. ^[2] ; Donadi, Eduardo A. ^[3] ; Passos, Geraldo A. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Genet, Mol Immunogenet Grp, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Philosophy Sci & Letters, Dept Biol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Clin Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Disciplines Genet & Mol Biol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Immunobiology; v. 220, n. 1, p. 93-102, JAN 2015.
• Web of Science Citations: 10

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. (C) 2014 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/17481-1 - The function of the AIRE gene and of Micro RNAs in the control of adhesion between medullary thymic epithelial cells with thymocytes
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/56594-8 - Control of the transcriptome in diabetes mellitus
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support Opportunities: Research Projects - Thematic Grants