Direct and indirect roles of the LTbetaR pathway in central tolerance induction

Trends Immunol. 2010 Sep;31(9):325-31. doi: 10.1016/j.it.2010.06.005. Epub 2010 Aug 2.

Abstract

Medullary thymic epithelial cells (mTECs) play a critical role in thymic negative selection of autoreactive thymocytes, especially for thymocytes specific for peripheral tissue-restricted self-antigens (TRA). Deficiency in lymphotoxin b receptor (LTbetaR) is associated with peripheral tissue inflammation, but whether this is caused by defective negative selection has been unclear; the significance of the LTbetaR pathway for negative selection is evident in some models but not others. Here, we revisit the data and clarify the role of LTbetaR in mTEC development and function and thymic TRA expression. These processes are discussed as potential mechanisms for LTbetaR-mediated control of negative selection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Humans
  • Immune Tolerance*
  • Lymphotoxin beta Receptor / immunology*
  • Lymphotoxin beta Receptor / metabolism
  • Signal Transduction*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Lymphotoxin beta Receptor