Human neutrophils in auto-immunity

Thieblemont, Nathalie, Wright, Helen L ORCID: 0000-0003-0442-3134, Edwards, Steven W ORCID: 0000-0002-7074-0552 and Witko-Sarsat, Veronique (2016) Human neutrophils in auto-immunity. SEMINARS IN IMMUNOLOGY, 28 (2). pp. 159-173.

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Abstract

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity.

Item Type:	Article
Uncontrolled Keywords:	Neutrophils, Vasculitis, Rheumatoid arthritis, Lupus, Apoptosis, Phagocytosis
Depositing User:	Symplectic Admin
Date Deposited:	06 Apr 2016 14:22
Last Modified:	16 Dec 2022 12:54
DOI:	10.1016/j.smim.2016.03.004
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3000037