title: Aire-dependent peripheral tissue antigen mRNAs in mTEC cells feature networking refractoriness to microRNA interaction.
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.
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Macedo
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Ernna H
authors.initials: EH
authors.lastname: Oliveira
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Almeida
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Donate
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Thaís A
authors.initials: TA
authors.lastname: Fornari
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pezzi
authors.affiliation: Department of Biology, Faculty of Philosophy, Sciences and Letters, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Elza T
authors.initials: ET
authors.lastname: Sakamoto-Hojo
authors.affiliation: Department of Clinical Medicine, School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil; Department of Morphology, Physiology and Basic Pathology, Disciplines of Genetics and Molecular Biology, School of Dentistry of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil. Electronic address: passos@usp.br.
authors.forename: Geraldo A
authors.initials: GA
authors.lastname: Passos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics* / Q000276:immunology; D016000:Cluster Analysis; D004843:Epistasis, Genetic; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D017634:Self Tolerance; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000096927:AIRE Protein
chemical_list: D000941:Antigens; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D000096927:AIRE Protein
keywords: Aire gene; Peripheral tissue antigen; Post-transcriptional control; Self-tolerance; Thymus; microRNAs