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

doi:10.1038/nm1590

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 journal › Review article › peer-review

389 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 language	English (US)
Pages (from-to)	543-551
Number of pages	9
Journal	Nature medicine
Volume	13
Issue number	5
DOIs	https://doi.org/10.1038/nm1590
State	Published - May 2007

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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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.",

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AU - Beutler, Bruce

AU - Theofilopoulos, Argyrios N.

PY - 2007/5

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N2 - 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.

AB - 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.

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

Abstract

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