Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.
The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and claudin-4 (Cld3,4) were 'preferentially' expressed in Aire(+) mTECs. In early ontogeny, Cld3,4(hi) TECs derived from the most apical layer of the stratified thymic anlage first expressed known mTEC markers such as UEA-1 ligand and MTS10. We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF-kappaB-inducing kinase and the adaptor molecule TRAF6. Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis.
Hamazaki
Yoko
Y
Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Fujita
Harumi
H
Kobayashi
Takashi
T
Choi
Yongwon
Y
Scott
Hamish S
HS
Matsumoto
Mitsuru
M
Minato
Nagahiro
N
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D062465:Claudin-3; D062506:Claudin-4; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D062793:Occludin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
D062465:Claudin-3; D062506:Claudin-4; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D062793:Occludin; D014157:Transcription Factors; D000096927:AIRE Protein; C568123:Cldn3 protein, mouse; C568158:Cldn4 protein, mouse; C568986:Ocln protein, mouse