Cross-regulation of TNF and IFN-α in autoimmune diseases

A. Karolina Palucka, Jean Philippe Blanck, Lynda Bennett, Virginia Pascual, Jacques Banchereau

Research output: Contribution to journalArticle

372 Scopus citations

Abstract

Cytokines, most particularly TNF and type I IFN (IFN-αβ), have been long considered essential elements in the development of autoimmunity. Identification of TNF in the pathogenesis of rheumatoid arthritis and TNF antagonist therapy represent successes of immunology. IFN-αβ plays a major role in systemic lupus erythematosus (SLE), a prototype autoimmune disease characterized by a break of tolerance to nuclear components. Here, we show that TNF regulates IFN-α production in vitro at two levels. First, it inhibits the generation of plasmacytoid dendritic cells (pDCs), a major producer of IFN-αβ, from CD34+ hematopoietic progenitors. Second, it inhibits IFN-α release by immature pDCs exposed to influenza virus. Neutralization of endogenous TNF sustains IFN-α secretion by pDCs. These findings are clinically relevant, as five of five patients with systemic juvenile arthritis treated with TNF antagonists display overexpression of IFN-α-regulated genes in their blood leukocytes. These results, therefore, might provide a mechanistic explanation for the development of anti-dsDNA antibodies and lupus-like syndrome in patients undergoing anti-TNF therapy.

Original languageEnglish (US)
Pages (from-to)3372-3377
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Keywords

  • Autoimmunity
  • Cytokines
  • Dendritic cells

ASJC Scopus subject areas

  • General

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