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Seminars in Immunopathology

, Volume 35, Issue 4, pp 465–480 | Cite as

Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity

  • Marko RadicEmail author
  • Tony N. Marion
Review

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 

Notes

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.

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Microbiology, Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisUSA

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