Dependence of self-tolerance on TRAF6-directed development of thymic stroma

Science. 2005 Apr 8;308(5719):248-51. doi: 10.1126/science.1105677. Epub 2005 Feb 10.


The microenvironments of the thymus are generated by thymic epithelial cells (TECs) and are essential for inducing immune self-tolerance or developing T cells. However, the molecular mechanisms that underlie the differentiation of TECs and thymic compartmentalization are not fully understood. Here we show that deficiency in the tumor necrosis factor receptor-associated factor (TRAF) 6 results in disorganized distribution of medullary TECs (mTECs) and the absence of mature mTECs. Engraftment of thymic stroma of TRAF6(-/-) embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Line
  • Epithelial Cells / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Organ Culture Techniques
  • Proto-Oncogene Proteins / physiology
  • Self Tolerance*
  • T-Lymphocytes / immunology
  • TNF Receptor-Associated Factor 6 / immunology
  • TNF Receptor-Associated Factor 6 / physiology*
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / immunology*
  • Transcription Factor RelB
  • Transcription Factors / physiology


  • Proto-Oncogene Proteins
  • Relb protein, mouse
  • TNF Receptor-Associated Factor 6
  • Transcription Factors
  • Transcription Factor RelB