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

Nat Med. 2007 May;13(5):543-51. doi: 10.1038/nm1590.


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.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / physiopathology
  • Autoimmunity / physiology*
  • Humans
  • Interferon Type I / immunology*
  • Interferon-alpha / immunology
  • Interferon-beta / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Models, Immunological
  • Toll-Like Receptors / immunology*


  • Interferon Type I
  • Interferon-alpha
  • Toll-Like Receptors
  • Interferon-beta