The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases

Citrullination of proteins is crucial for the formation of neutrophil extracellular traps (NETs) – strands of nuclear DNA expulsed in the extracellular environment along with antimicrobial proteins in order to halt the spread of pathogens. Paradoxically, NETs may be immunogenic and contribute to inf...

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Main Authors: Martin Maronek, Roman Gardlik
Format: Article
Language:English
Published: Karger Publishers 2022-03-01
Series:Journal of Innate Immunity
Subjects:
Online Access:https://www.karger.com/Article/FullText/522331
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author Martin Maronek
Roman Gardlik
author_facet Martin Maronek
Roman Gardlik
author_sort Martin Maronek
collection DOAJ
description Citrullination of proteins is crucial for the formation of neutrophil extracellular traps (NETs) – strands of nuclear DNA expulsed in the extracellular environment along with antimicrobial proteins in order to halt the spread of pathogens. Paradoxically, NETs may be immunogenic and contribute to inflammation. It is known that for the externalization of DNA, a group of enzymes called peptidyl arginine deiminases (PADs) is required. Current research often looks at citrullination, NET formation, PAD overexpression, and extracellular DNA (ecDNA) accumulation in chronic diseases as separate events. In contrast, we propose that citrullination can be viewed as the primary mechanism of autoimmunity, for instance by the formation of anti-citrullinated protein antibodies (ACPAs) but also as a process contributing to chronic inflammation. Therefore, citrullination could be at the center, connecting and impacting multiple inflammatory diseases in which ACPAs, NETs, or ecDNA have already been documented. In this review, we aimed to highlight the importance of citrullination in the etiopathogenesis of a number of chronic diseases and to explore the diagnostic, prognostic, and therapeutic potential of the citrullination-NET axis.
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spelling doaj.art-33d5f1fe96cf4ac992a96f7136d41d182022-12-22T02:26:57ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282022-03-0112510.1159/000522331522331The Citrullination-Neutrophil Extracellular Trap Axis in Chronic DiseasesMartin MaronekRoman GardlikCitrullination of proteins is crucial for the formation of neutrophil extracellular traps (NETs) – strands of nuclear DNA expulsed in the extracellular environment along with antimicrobial proteins in order to halt the spread of pathogens. Paradoxically, NETs may be immunogenic and contribute to inflammation. It is known that for the externalization of DNA, a group of enzymes called peptidyl arginine deiminases (PADs) is required. Current research often looks at citrullination, NET formation, PAD overexpression, and extracellular DNA (ecDNA) accumulation in chronic diseases as separate events. In contrast, we propose that citrullination can be viewed as the primary mechanism of autoimmunity, for instance by the formation of anti-citrullinated protein antibodies (ACPAs) but also as a process contributing to chronic inflammation. Therefore, citrullination could be at the center, connecting and impacting multiple inflammatory diseases in which ACPAs, NETs, or ecDNA have already been documented. In this review, we aimed to highlight the importance of citrullination in the etiopathogenesis of a number of chronic diseases and to explore the diagnostic, prognostic, and therapeutic potential of the citrullination-NET axis.https://www.karger.com/Article/FullText/522331citrullinationneutrophil extracellular trapsautoimmune diseasemetabolic diseasecardiovascular disease
spellingShingle Martin Maronek
Roman Gardlik
The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
Journal of Innate Immunity
citrullination
neutrophil extracellular traps
autoimmune disease
metabolic disease
cardiovascular disease
title The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
title_full The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
title_fullStr The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
title_full_unstemmed The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
title_short The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
title_sort citrullination neutrophil extracellular trap axis in chronic diseases
topic citrullination
neutrophil extracellular traps
autoimmune disease
metabolic disease
cardiovascular disease
url https://www.karger.com/Article/FullText/522331
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