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Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin


Hamazaki, Y; Fujita, H; Kobayashi, T; Choi, Y; Scott, HS; Matsumoto, M; Minato, N
2007-03
NATURE IMMUNOLOGY
Journal Article
8
3
304-311
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-kappa B-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.
NATURE PUBLISHING GROUP
PROMISCUOUS GENE-EXPRESSION; CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; TIGHT JUNCTION STRANDS; CENTRAL TOLERANCE; SELF-TOLERANCE; DEFICIENT MICE; ANTIGEN; DIFFERENTIATION; AUTOIMMUNITY; PROGENITOR
10.1038/ni1438
Refer to copyright notice on published article.

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Creation Date 2007-03-01 12:00:00