TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity
Top Cited Papers
- 3 May 2007
- journal article
- review article
- Published by Springer Nature in Nature Medicine
- Vol. 13 (5) , 543-551
- https://doi.org/10.1038/nm1590
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.Keywords
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