"NETtling" the host: Breaking of tolerance in chronic inflammation and chronic infection

Journal of Autoimmunity
Sladjana Skopelja-GardnerWilliam Fc Rigby

Abstract

How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i.e. citrullinated and carbamylated proteins targeted by anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein antibodies (ACarPA), respectively, localize to the NETs. Moreover, NETs provide stimuli to dendritic cells that potentiate adaptive autoimmune responses. However, while NETs promote inflammation and appear to induce humoral autoreactivity across autoimmune diseases, the antigen specificity of autoantibodies found in these disorders is striking. These unique autoantigen signatures suggest that not all NETs are created equal and that the environmen...Continue Reading

Citations

Aug 11, 2019·Nature Reviews. Nephrology·Anjali A SatoskarTibor Nadasdy
Dec 28, 2019·Journal of the American Society of Nephrology : JASN·Marilina AntonelouUNKNOWN RAVE-ITN Investigators
May 1, 2018·Cellular & Molecular Immunology·Bo LiXiong Ma
Jan 23, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jan Willem Cohen Tervaert
Jan 10, 2019·Journal of Immunology Research·Weiqian ChenJin Lin
Aug 6, 2019·Frontiers in Immunology·Sladjana Skopelja-GardnerWilliam F C Rigby
Dec 19, 2019·Frontiers in Immunology·Vanessa GrangerLuc de Chaisemartin
Jul 8, 2020·International Journal of Molecular Sciences·Elif Damla ArisanSigrun Lange
Jan 1, 2020·International Journal of Molecular Sciences·Yoshie KametaniYutaka Tokuda
Jul 3, 2019·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·J TheprungsirikulW F C Rigby
Jun 19, 2021·Journal of Translational Autoimmunity·Jomkuan TheprungsirikulWilliam F C Rigby
Jan 15, 2019·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Ruchi YadavBalázs Rada

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