Article abstract
Nature Immunology 8, 304 - 311 (2007)
Published online: 4 February 2007 | doi:10.1038/ni1438
Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin
Yoko Hamazaki1, Harumi Fujita2, Takashi Kobayashi3, Yongwon Choi4, Hamish S Scott5, Mitsuru Matsumoto6 & Nagahiro Minato1,2
Abstract
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, Cld3,4hi 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 Cld3,4hi UEA-1+ TECs represented the initial progenitors specified for Aire+ mTECs, whose development crucially required NF-
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.
- Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
- Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
- Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
- Department of Pathology and Lab Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
- The Walter and Eliza Hall Institute of Medical Research, 3050 Victoria, Australia.
- Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan.
Correspondence to: Nagahiro Minato1,2 e-mail: minato@imm.med.kyoto-u.ac.jp
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