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 language | English (US) |
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Pages (from-to) | 267-278 |
Number of pages | 12 |
Journal | Journal of Molecular Medicine |
Volume | 83 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2005 |
Keywords
- Anergy
- Apoptosis
- Autoimmunity
- Immunotherapy
- Lupus
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Genetics(clinical)