T-helper cell intrinsic defects in lupus that break peripheral tolerance to nuclear autoantigens

Syamal K. Datta*, Li Zhang, Luting Xu

*Corresponding author for this work

Research output: Contribution to journalReview article

29 Scopus citations

Abstract

Special populations of T helper cells drive B cells to produce IgG class switched, pathogenic autoantibodies in lupus. The major source of antigenic determinants (epitopes) that trigger interactions between lupus T and B cells is nucleosomes of apoptotic cells. These epitopes can be used for antigen-specific therapy of lupus. Secondly, the autoimmune T cells of lupus are sustained because they resist anergy and activation-induced programmed cell death by markedly upregulating cyclooxygenase (COX) 2 along with the antiapoptotic molecule c-FLIP. Only certain COX-2 inhibitors block pathogenic anti-DNA autoantibody production in lupus by causing death of autoimmune T helper cells. Hence COX-2 inhibitors may work independently of their ability to block the enzymatic function of COX-2, and structural peculiarities of these select inhibitors may lead to better drug discovery and design.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalJournal of Molecular Medicine
Volume83
Issue number4
DOIs
Publication statusPublished - Apr 1 2005

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Keywords

  • Anergy
  • Apoptosis
  • Autoimmunity
  • Immunotherapy
  • Lupus

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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