title: Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors.
abstract: In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of first cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κB (RANK). In vivo analysis reveals the capacity of CD205(+) TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire(+) mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts.
authors.affiliation: MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Song
authors.initials: S
authors.lastname: Baik
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: William E
authors.initials: WE
authors.lastname: Jenkinson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D015703:Antigens, CD; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000096927:AIRE Protein; C093569:DEC-205 receptor