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

403 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

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1038/nm1590

Cite this

@article{66835f67fb25406e91192225b2253f41,

title = "TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity",

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.",

author = "Roberto Baccala and Kasper Hoebe and Kono, {Dwight H.} and Bruce Beutler and Theofilopoulos, {Argyrios N.}",

year = "2007",

month = may,

doi = "10.1038/nm1590",

language = "English (US)",

volume = "13",

pages = "543--551",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity

AU - Baccala, Roberto

AU - Hoebe, Kasper

AU - Kono, Dwight H.

AU - Beutler, Bruce

AU - Theofilopoulos, Argyrios N.

PY - 2007/5

Y1 - 2007/5

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.

UR - http://www.scopus.com/inward/record.url?scp=34249707811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249707811&partnerID=8YFLogxK

U2 - 10.1038/nm1590

DO - 10.1038/nm1590

M3 - Review article

C2 - 17479100

AN - SCOPUS:34249707811

SN - 1078-8956

VL - 13

SP - 543

EP - 551

JO - Nature medicine

JF - Nature medicine

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this