Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity
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Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity Marko Radic & Tony N. Marion
Received: 9 January 2013 / Accepted: 18 March 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases. Keywords Systemic lupus erythematosus . Musculoskeletal disorders . Glomerulonephritis . Antigen selection . Neutrophil extracellular traps . Tolerance
Autoimmunity Autoimmune disorders are relatively common disturbances of the immune system [1]. Autoimmunity arises from a This article is a contribution to the special issue on Neutrophils - Guest Editors: Paul Hasler and Sinuhe Hahn M. Radic (*) : T. N. Marion Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA e-mail: [email protected]
disruption of the instructive mechanisms that ensure tolerance, i.e., the active avoidance of self-reactivity by the immune system [2]. Tolerance relies on the continuous instruction of the immune system to recognize, yet remain inert, against molecules that are expressed by the host organism. In autoimmune diseases, tolerance is disturbed and the immune system reacts against particular self-antigens. Why certain autoantigens fail to be regulated by tolerance and instead stimulate the immune response is poorly understood. The initial events that induce anti-self reactivity are therefore an important focus of immunology research. Once autoimmune reactivity is initiated, the continuous supply of autoantigens perpetuates the stimulation of the immune system. Over time, excessive formation of immune complexes and/or reactivity against components of the extracellular matrix lead to tissue damage and clinical signs of autoimmune diseases [3]. Different autoimmune diseases can be distinguished by the specific targets of autoimmune reactions and the clinical symptoms that arise as a consequence of autoreactivity [4]. Systemic autoimmune diseases are a group of related musc
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