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Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity

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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.

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Acknowledgments

The authors acknowledge the research support from the Lupus Research Institute of New York, the National Institutes of Health grants AI26833 and RR301812, and the UTHSC Center of Excellence for Diseases of Connective Tissues. The authors gratefully acknowledge the expert assistance of Mr. Tim Higgins, Senior Illustrator.

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The authors declare that they have no conflict of interest.

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  1. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN, 38163, USA

    Marko Radic & Tony N. Marion

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Correspondence to Marko Radic.

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This article is a contribution to the special issue on Neutrophils - Guest Editors: Paul Hasler and Sinuhe Hahn

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Radic, M., Marion, T.N. Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity. Semin Immunopathol 35, 465–480 (2013). https://doi.org/10.1007/s00281-013-0376-6

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