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

被引:165
作者
Hamazaki, Yoko
Fujita, Harumi
Kobayashi, Takashi
Choi, Yongwon
Scott, Hamish S.
Matsumoto, Mitsuru
Minato, Nagahiro [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan
[2] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan
[3] Kyushu Univ, Med Inst Bioregulat, Fukuoka 8128582, Japan
[4] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[5] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[6] Univ Tokushima, Inst Enzyme Res, Tokushima 7708503, Japan
关键词
D O I
10.1038/ni1438
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:304 / 311
页数:8
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