Toll-Like Receptors, Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by autoantibodies targeting nucleic acids and nuclear proteins. Circulating self-antigen immune complexes (ICs) from patients with SLE have been shown to have adjuvant-like properties that can directly or indirectly hyperstimulate autoreactive lymphocytes. These adjuvant-like complexes are composed of DNA and/or RNA bound to self-derived protein antigens and immunoglobulin (Ig) G. Recently, nucleic acid-containing ICs were shown to activate leukocytes via engagement of the innate immune nucleic acid sensors Toll-like receptors 7, 8 (TLR7, TLR8) (ssRNA), and TLR9 (DNA), resulting in the production of interferon-alpha (IFN-α) and other inflammatory cytokines. Based on these observations, it is believed that TLR7, TLR8, and TLR9 pathway activations are central to the development of inflammation in human lupus. This chapter will focus on the role of these TLR family members in the susceptibility, initiation, and exacerbation of SLE in mice and humans.