TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity.
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.
Baccala
Roberto
R
The Scripps Research Institute, Department of Immunology, La Jolla, California 93037, USA.
Hoebe
Kasper
K
Kono
Dwight H
DH
Beutler
Bruce
B
Theofilopoulos
Argyrios N
AN
D001327:Autoimmune Diseases / Q000503:physiopathology; D015551:Autoimmunity / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology; D018448:Models, Immunological; D051193:Toll-Like Receptors / Q000276:immunology*
D007370:Interferon Type I; D016898:Interferon-alpha; D051193:Toll-Like Receptors; D016899:Interferon-beta