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

Academic Article
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Overview

authors

  • BaccalĂ , Roberto
  • Hoebe, K.
  • Kono, Dwight
  • Beutler, Bruce
  • Theofilopoulos, Argyrios

publication date

  • 2007

journal

  • Nature Medicine  Journal

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.

subject areas

  • Autoimmune Diseases
  • Autoimmunity
  • Humans
  • Interferon Type I
  • Interferon-alpha
  • Interferon-beta
  • Lupus Erythematosus, Systemic
  • Models, Immunological
  • Toll-Like Receptors
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Identity

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1590

PubMed ID

  • 17479100
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Additional Document Info

start page

  • 543

end page

  • 551

volume

  • 13

issue

  • 5

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