Promiscuous gene expression in the thymus: the root of central tolerance.
The thymus is a complex organ with an epithelium formed by two main cell types, the cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs), referred to as stroma. Immature thymocytes arising from the bone marrow, macrophages and dendritic cells also populate the thymus. Thymocytes evolve to mature T cells featuring cell differentiation antigens (CDs), which characterize the phenotypically distinct stages, defined as double-negative (DN), double positive (DP) and single positive (SP), based on expression of the coreceptors CD4 and CD8. The thymus is therefore implicated in T cell differentiation and during development into T cells thymocytes are in close association with the stroma. Recent evidence showed that mTECs express a diverse set of genes coding for parenchymal organ specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has led to the reconsideration of the role of the thymus in central T cell tolerance to self-antigens, which prevents autoimmunity. The evidence of PGE is causing a reanalysis in the scope of central tolerance understanding. We summarize the evidence of PGE in the thymus, focusing particularly the use of cDNA microarray technology for the broad characterization of gene expression and demarcation of PGE emergence during thymus ontogeny.
Magalhães
Danielle A R
DA
Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine, University of São Paulo (USP), 14040-900 Ribeirão Preto, SP, Brazil.
Silveira
Eduardo L V
EL
Junta
Cristina M
CM
Sandrin-Garcia
Paula
P
Fachin
Ana Lucia
AL
Donadi
Eduardo A
EA
Sakamoto-Hojo
Elza T
ET
Passos
Geraldo A S
GA
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens