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.
authors.affiliation: The Scripps Research Institute, Department of Immunology, La Jolla, California 93037, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Baccala
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Dwight H
authors.initials: DH
authors.lastname: Kono
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Argyrios N
authors.initials: AN
authors.lastname: Theofilopoulos
mesh_terms: 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*
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D051193:Toll-Like Receptors; D016899:Interferon-beta