title: The innate immune system in human systemic lupus erythematosus.
abstract: Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Weidenbusch
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Hyderabad 500 078, India.
authors.forename: Onkar P
authors.initials: OP
authors.lastname: Kulkarni
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany hjanders@med.uni-muenchen.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000627:therapeutic use; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D058990:Molecular Targeted Therapy / Q000379:methods; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D007370:Interferon Type I; D051192:Receptors, Pattern Recognition
keywords: autoimmunity; glomerulonephritis; inflammation; lupus nephritis; toll-like receptors