TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity

Roberto Baccala, Kasper Hoebe, Dwight H. Kono, Bruce Beutler, Argyrios N. Theofilopoulos

Research output: Contribution to journalReview article

355 Scopus citations

Abstract

We formulate a two-phase paradigm of autoimmunity associated with systemic lupus erythematosus, the archetypal autoimmune disease. The initial Toll-like receptor (TLR)-independent phase is mediated by dendritic cell uptake of apoptotic cell debris and associated nucleic acids, whereas the subsequent TLR-dependent phase serves an amplification function and is mediated by uptake of TLR ligands derived from self-antigens (principally nucleic acids) complexed with autoantibodies. Both phases depend on elaboration of type I interferons (IFNs), and therapeutic interruption of induction or activity of these cytokines in predisposed individuals might have a substantial mitigating effect in lupus and other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)543-551
Number of pages9
JournalNature medicine
Volume13
Issue number5
DOIs
StatePublished - May 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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