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

Nat Immunol. 2007 Mar;8(3):304-11. doi: 10.1038/ni1438. Epub 2007 Feb 4.

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, Cld3,4(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage
  • Claudin-3
  • Claudin-4
  • Embryo, Mammalian
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Histocompatibility Antigens Class II / metabolism
  • Immunohistochemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Occludin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymus Gland / cytology*
  • Thymus Gland / embryology
  • Thymus Gland / growth & development
  • Tight Junctions / metabolism
  • Transcription Factors / metabolism*

Substances

  • APECED protein
  • Claudin-3
  • Claudin-4
  • Cldn3 protein, mouse
  • Cldn4 protein, mouse
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • Occludin
  • Ocln protein, mouse
  • Transcription Factors