title: Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program.
abstract: Understanding the cellular dynamics of Aire-expressing lineage(s) among medullary thymic epithelial cells (AEL-mTECs) is essential for gaining insight into the roles of Aire in establishment of self-tolerance. In this study, we monitored the maturation program of AEL-mTECs by temporal lineage tracing, in which bacterial artificial chromosome transgenic mice expressing tamoxifen-inducible Cre recombinase under control of the Aire regulatory element were crossed with reporter strains. We estimated that the half-life of AEL-mTECs subsequent to Aire expression was ∼7-8 d, which was much longer than that reported previously, owing to the existence of a post-Aire stage. We found that loss of Aire did not alter the overall lifespan of AEL-mTECs, inconsistent with the previous notion that Aire expression in medullary thymic epithelial cells (mTECs) might result in their apoptosis for efficient cross-presentation of self-antigens expressed by AEL-mTECs. In contrast, Aire was required for the full maturation program of AEL-mTECs, as exemplified by the lack of physiological downregulation of CD80 during the post-Aire stage in Aire-deficient mice, thus accounting for the abnormally increased CD80(high) mTECs seen in such mice. Of interest, increased CD80(high) mTECs in Aire-deficient mice were not mTEC autonomous and were dependent on cross-talk with thymocytes. These results further support the roles of Aire in the differentiation program of AEL-mTECs.
authors: Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan;
authors: Yumiko
authors: Y
authors: Nishikawa
authors: Hitoshi
authors: H
authors: Nishijima
authors: Minoru
authors: M
authors: Matsumoto
authors: Junko
authors: J
authors: Morimoto
authors: Fumiko
authors: F
authors: Hirota
authors: Satoru
authors: S
authors: Takahashi
authors: Hervé
authors: H
authors: Luche
authors: Hans Joerg
authors: HJ
authors: Fehling
authors: Yasuhiro
authors: Y
authors: Mouri
authors: Mitsuru
authors: M
authors: Matsumoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D001324:Autoantigens; D018122:B7-1 Antigen; D008164:Luminescent Proteins; D014157:Transcription Factors; D000096927:AIRE Protein