Neutrophil Extracellular Traps in the Autoimmunity Context
The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by prot...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-03-01
|
Series: | Frontiers in Medicine |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.614829/full |
id |
doaj-20c3bfefbfb24d8ebca38de4762c32b5 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maurizio Bruschi Gabriella Moroni Renato Alberto Sinico Franco Franceschini Micaela Fredi Augusto Vaglio Lorenzo Cavagna Andrea Petretto Federico Pratesi Paola Migliorini Angelo Manfredi Giuseppe A. Ramirez Pasquale Esposito Simone Negrini Barbara Trezzi Giacomo Emmi Domenico Santoro Francesco Scolari Stefano Volpi Marta Mosca Angela Tincani Giovanni Candiano Marco Prunotto Enrico Verrina Andrea Angeletti Angelo Ravelli Gian Marco Ghiggeri Gian Marco Ghiggeri |
spellingShingle |
Maurizio Bruschi Gabriella Moroni Renato Alberto Sinico Franco Franceschini Micaela Fredi Augusto Vaglio Lorenzo Cavagna Andrea Petretto Federico Pratesi Paola Migliorini Angelo Manfredi Giuseppe A. Ramirez Pasquale Esposito Simone Negrini Barbara Trezzi Giacomo Emmi Domenico Santoro Francesco Scolari Stefano Volpi Marta Mosca Angela Tincani Giovanni Candiano Marco Prunotto Enrico Verrina Andrea Angeletti Angelo Ravelli Gian Marco Ghiggeri Gian Marco Ghiggeri Neutrophil Extracellular Traps in the Autoimmunity Context Frontiers in Medicine Lupus nephritis systemic lupu erythematosus biomarker anti-histone anti-alpha enolase anti-C1q antibodies |
author_facet |
Maurizio Bruschi Gabriella Moroni Renato Alberto Sinico Franco Franceschini Micaela Fredi Augusto Vaglio Lorenzo Cavagna Andrea Petretto Federico Pratesi Paola Migliorini Angelo Manfredi Giuseppe A. Ramirez Pasquale Esposito Simone Negrini Barbara Trezzi Giacomo Emmi Domenico Santoro Francesco Scolari Stefano Volpi Marta Mosca Angela Tincani Giovanni Candiano Marco Prunotto Enrico Verrina Andrea Angeletti Angelo Ravelli Gian Marco Ghiggeri Gian Marco Ghiggeri |
author_sort |
Maurizio Bruschi |
title |
Neutrophil Extracellular Traps in the Autoimmunity Context |
title_short |
Neutrophil Extracellular Traps in the Autoimmunity Context |
title_full |
Neutrophil Extracellular Traps in the Autoimmunity Context |
title_fullStr |
Neutrophil Extracellular Traps in the Autoimmunity Context |
title_full_unstemmed |
Neutrophil Extracellular Traps in the Autoimmunity Context |
title_sort |
neutrophil extracellular traps in the autoimmunity context |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2021-03-01 |
description |
The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE.Clinical Trial Registration Number: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115). |
topic |
Lupus nephritis systemic lupu erythematosus biomarker anti-histone anti-alpha enolase anti-C1q antibodies |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2021.614829/full |
work_keys_str_mv |
AT mauriziobruschi neutrophilextracellulartrapsintheautoimmunitycontext AT gabriellamoroni neutrophilextracellulartrapsintheautoimmunitycontext AT renatoalbertosinico neutrophilextracellulartrapsintheautoimmunitycontext AT francofranceschini neutrophilextracellulartrapsintheautoimmunitycontext AT micaelafredi neutrophilextracellulartrapsintheautoimmunitycontext AT augustovaglio neutrophilextracellulartrapsintheautoimmunitycontext AT lorenzocavagna neutrophilextracellulartrapsintheautoimmunitycontext AT andreapetretto neutrophilextracellulartrapsintheautoimmunitycontext AT federicopratesi neutrophilextracellulartrapsintheautoimmunitycontext AT paolamigliorini neutrophilextracellulartrapsintheautoimmunitycontext AT angelomanfredi neutrophilextracellulartrapsintheautoimmunitycontext AT giuseppearamirez neutrophilextracellulartrapsintheautoimmunitycontext AT pasqualeesposito neutrophilextracellulartrapsintheautoimmunitycontext AT simonenegrini neutrophilextracellulartrapsintheautoimmunitycontext AT barbaratrezzi neutrophilextracellulartrapsintheautoimmunitycontext AT giacomoemmi neutrophilextracellulartrapsintheautoimmunitycontext AT domenicosantoro neutrophilextracellulartrapsintheautoimmunitycontext AT francescoscolari neutrophilextracellulartrapsintheautoimmunitycontext AT stefanovolpi neutrophilextracellulartrapsintheautoimmunitycontext AT martamosca neutrophilextracellulartrapsintheautoimmunitycontext AT angelatincani neutrophilextracellulartrapsintheautoimmunitycontext AT giovannicandiano neutrophilextracellulartrapsintheautoimmunitycontext AT marcoprunotto neutrophilextracellulartrapsintheautoimmunitycontext AT enricoverrina neutrophilextracellulartrapsintheautoimmunitycontext AT andreaangeletti neutrophilextracellulartrapsintheautoimmunitycontext AT angeloravelli neutrophilextracellulartrapsintheautoimmunitycontext AT gianmarcoghiggeri neutrophilextracellulartrapsintheautoimmunitycontext AT gianmarcoghiggeri neutrophilextracellulartrapsintheautoimmunitycontext |
_version_ |
1724209589590687744 |
spelling |
doaj-20c3bfefbfb24d8ebca38de4762c32b52021-03-22T04:40:33ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-03-01810.3389/fmed.2021.614829614829Neutrophil Extracellular Traps in the Autoimmunity ContextMaurizio Bruschi0Gabriella Moroni1Renato Alberto Sinico2Franco Franceschini3Micaela Fredi4Augusto Vaglio5Lorenzo Cavagna6Andrea Petretto7Federico Pratesi8Paola Migliorini9Angelo Manfredi10Giuseppe A. Ramirez11Pasquale Esposito12Simone Negrini13Barbara Trezzi14Giacomo Emmi15Domenico Santoro16Francesco Scolari17Stefano Volpi18Marta Mosca19Angela Tincani20Giovanni Candiano21Marco Prunotto22Enrico Verrina23Andrea Angeletti24Angelo Ravelli25Gian Marco Ghiggeri26Gian Marco Ghiggeri27Laboratory of Molecular Nephrology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDivision of Nephrology and Dialysis Fondazione IRCCS Ca' Granda Ospedale Maggiore, Milan, ItalyDepartment of Medicine and Surgery, University of Milan, Bicocca, ItalyRheumatology and Clinical Immunology, ASST Spedali Civili and Università of Brescia, Brescia, ItalyRheumatology and Clinical Immunology, ASST Spedali Civili and Università of Brescia, Brescia, ItalyDepartment of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Firenze, and Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, ItalyDivision of Rheumatology, University and IRCCS Policlinico S. Matteo, Pavia, ItalyCore Facilities-Proteomics Laboratory, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, ItalyClinical Immunology Unit, Department of Internal Medicine, University of Pisa, Pisa, ItalyClinical Immunology Unit, Department of Internal Medicine, University of Pisa, Pisa, ItalyUnit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Milan, ItalyUnit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Milan, Italy0Division of Nephrology, University of Genoa and Policlinico San Martino, Genoa, Italy1Department of Internal Medicine, University of Genoa, Genoa, ItalyDepartment of Medicine and Surgery, University of Milan, Bicocca, Italy2Lupus Clinic Department of Biomedicine, University of Florence, University Hospital Careggi, Florence, Italy3Nephrology and Dialysis Unit, University of Messina and G. Martino Hospital, Messina, Italy4Division of Nephrology and Dialysis, University of Brescia and Ospedale di Montichiari, Brescia, Italy5Division of Paediatric Rheumatology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy6Rheumatologu Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyRheumatology and Clinical Immunology, ASST Spedali Civili and Università of Brescia, Brescia, ItalyLaboratory of Molecular Nephrology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy7School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland8Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy8Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy5Division of Paediatric Rheumatology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, ItalyLaboratory of Molecular Nephrology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy8Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, ItalyThe formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE.Clinical Trial Registration Number: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).https://www.frontiersin.org/articles/10.3389/fmed.2021.614829/fullLupus nephritissystemic lupu erythematosusbiomarkeranti-histoneanti-alpha enolaseanti-C1q antibodies |