AUTHOR=Bruschi Maurizio , Moroni Gabriella , Sinico Renato Alberto , Franceschini Franco , Fredi Micaela , Vaglio Augusto , Cavagna Lorenzo , Petretto Andrea , Pratesi Federico , Migliorini Paola , Manfredi Angelo , Ramirez Giuseppe A. , Esposito Pasquale , Negrini Simone , Trezzi Barbara , Emmi Giacomo , Santoro Domenico , Scolari Francesco , Volpi Stefano , Mosca Marta , Tincani Angela , Candiano Giovanni , Prunotto Marco , Verrina Enrico , Angeletti Andrea , Ravelli Angelo , Ghiggeri Gian Marco 

TITLE=Neutrophil Extracellular Traps in the Autoimmunity Context

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.614829

DOI=10.3389/fmed.2021.614829

ISSN=2296-858X

ABSTRACT=Formation of neutrophil extracellular traps (or NETs) is a strategy utilized by neutrophils for capturing infective agents. NETs consist  in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and virus are entrapped and killed by proteolysis. Several mechanisms contribute to de-condense nuclear chromatin and extrude nucleosome components from the neutrophil; once outside, DNA and DNA-protein complexes are recognized and presented to B-cells by Toll-like- receptor 9 (TLR9) that activate an immunologic response leading to the formation of IgG2 auto-antibody; in this context, NETs represent an antigenic source for autoimmunity. 
     There is a thin balance between production and removal of circulating NETs from blood that is necessary to avoid unwanted autoimmune reaction to NETs components here including the formation of anti-dsDNA antibodies. Circulating DNases 1 and IL3 are the two crucial enzymes for extracellular DNA removal. 
     Recent studies showed that circulating NETs are increased in Systemic Lupus Erythematosus (SLE) for a functional block of NETs removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations.  Persistence of free DNA or nucleosome components and oxidized proteins in circulating NETs may represent an important trigger to develop autoimmunity in SLE and be associated with the development of lupus nephritis. 
     Monitoring serum NET levels represent a potential  new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NETs formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE.