Molecular mimicry in innate immunity? The viral RNA recognition receptor TLR7 accelerates murine lupus.
Toll-like receptors (TLR), such as TLR7, were first described as innate pathogen recognition receptors that trigger appropriate antimicrobial immune responses upon exposure to pathogen-associated molecules, e.g. viral ssRNA. In parallel to ongoing studies on TLR-biology, mounting experimental evidence suggests that endogenous RNA-related autoantigens may also activate dendritic cells (DC) and B cells through TLR7. TLR7-mediated DC activation, autoantibody secretion, lymphoproliferation, and autoimmune tissue injury, are frequently observed in various murine models of systemic lupus and lupus nephritis. A paper in the current issue of the European Journal of Immunology, provide striking experimental evidence for this concept; the authors show that the Y chromosome-linked autoimmune accelerating (Yaa) translocation from the X-chromosome, consisting of 16 genes including Tlr7, largely mediates the autoimmune phenotype via the duplication of Tlr7. This finding highlights the need to address the significance of TLR7 in human lupus in terms of both genetic risk and as a therapeutic option.
Anders
Hans-Joachim
HJ
Medizinische Poliklinik, Ludwig Maximilians University Munich, Pettenkoferstrasse 8a, Munich, Germany. hjanders@med.uni-muenchen.de
Krug
Anne
A
Pawar
Rahul D
RD
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D018716:Molecular Mimicry; D012313:RNA / Q000276:immunology* / Q000378:metabolism; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; D001324:Autoantigens; D012367:RNA, Viral; D051199:Toll-Like Receptor 7; D012313:RNA