title: Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors.
abstract: Autoantigens that contain DNA, RNA, or self-IgG are preferred targets for autoantibodies in systemic lupus erythematosus (SLE). B cells promote SLE pathogenesis by producing autoantibodies, activating autoreactive T cells, and secreting cytokines. We discuss how certain autoreactive B cells are selectively activated, with emphasis on the roles of key Toll-like receptors (TLRs). Although TLR7, which recognizes ssRNA, promotes autoimmune disease, TLR9, which recognizes DNA, unexpectedly regulates disease, despite being required for the secretion of anti-chromatin autoantibodies. We describe positive feedback loops involving B cells, T cells, DCs, and soluble mediators, and how these networks are regulated by TLR signals.
authors.affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8035, United States. sean.christensen@yale.edu
authors.forename: Sean R
authors.initials: SR
authors.lastname: Christensen
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology*; D008213:Lymphocyte Activation; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D051193:Toll-Like Receptors