NF-κB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells

Baochun Zhang, Zhe Wang, Jane Ding, Pärt Peterson, William T. Gunning, Han Fei Ding

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Medullary thymic epithelial cells function as antigen-presenting cells in negative selection of self-reactive T cell clones, a process essential for the establishment of central self-tolerance. These cells mirror peripheral tissues through promiscuous expression of a diverse set of tissue-restricted self-antigens. The genes and signaling pathways that regulate the development of medullary thymic epithelial cells are not fully understood. Here we show that mice deficient in NF-κB2, a member of the NF-κB family, display a marked reduction in the number of mature medullary thymic epithelial cells that express CD80 and bind the lectin Ulex europaeus agglutinin-1, leading to a significant decrease in the extent of promiscuous gene expression in the thymus of NF-κB2-/- mice. Moreover, NF-κB2-/- mice manifest autoimmunity characterized by multiorgan infiltration of activated T cells and high levels of autoantibodies to multiple organs. A subpopulation of the mice also develops immune complex glomerulonephritis. These findings identify a physiological function of NF-κB2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction.

Original languageEnglish (US)
Pages (from-to)38617-38624
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number50
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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