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 journalArticle

346 Citations (Scopus)

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 2007

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Interferon Type I
Toll-Like Receptors
Autoimmunity
Nucleic Acids
Autoimmune Diseases
Autoantigens
Debris
Systemic Lupus Erythematosus
Autoantibodies
Dendritic Cells
Amplification
Cells
Cytokines
Ligands
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. / Baccala, Roberto; Hoebe, Kasper; Kono, Dwight H.; Beutler, Bruce; Theofilopoulos, Argyrios N.

In: Nature Medicine, Vol. 13, No. 5, 05.2007, p. 543-551.

Research output: Contribution to journalArticle

Baccala, Roberto ; Hoebe, Kasper ; Kono, Dwight H. ; Beutler, Bruce ; Theofilopoulos, Argyrios N. / TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. In: Nature Medicine. 2007 ; Vol. 13, No. 5. pp. 543-551.
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