Peckham, D orcid.org/0000-0001-7723-1868, Scambler, T, Savic, S orcid.org/0000-0001-7910-0554 et al. (1 more author) (2017) The burgeoning field of innate immune-mediated disease and autoinflammation. Journal of Pathology, 241 (2). pp. 123-139. ISSN 0022-3417
Abstract
Immune-mediated autoinflammatory diseases are occupying an increasingly prominent position among the pantheon of debilitating conditions that afflict mankind. This review focuses on some of the key developments which have occurred since the original description of autoinflammatory disease in 1999, and focuses on underlying mechanisms that trigger autoinflammation. The monogenic autoinflammatory disease range has expanded considerably during that time, and now includes a broad spectrum of disorders, including relatively common conditions such as cystic fibrosis and subsets of systemic lupus erythematosus. The innate immune system also plays a key role in the pathogenesis of complex inflammatory disorders. We have proposed a new nomenclature to accommodate the rapidly increasing number of monogenic disorders, which predispose to either autoinflammation or autoimmunity or, indeed, combinations of both. This new terminology also encompasses a wide spectrum of genetically determined autoinflammatory diseases, with variable clinical manifestations of immunodeficiency and immune dysregulation/autoimmunity. We also explore some of the ramifications of the breakthrough discovery of the physiologic role of pyrin and the search for identifiable factors that may serve to trigger attacks of autoinflammation. The evidence that pyrin, as part of the pyrin inflammasome, acts as a sensor of different inactivating bacterial modification Rho GTPases, rather than interacting directly with these microbial products, sets the stage for a better understanding of the role of micro-organisms and infections in the autoinflammatory disorders. Finally, we discuss some of the triggers of autoinflammation as well as potential therapeutic interventions aimed at enhancing autophagy and proteasome degradation pathways.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Peckham, D., Scambler, T., Savic, S. and McDermott, M. F. (2016), The burgeoning field of innate immune-mediated disease and autoinflammation. J. Pathol., which has been published in final form at https://doi.org/10.1002/path.4812. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | autoinflammatory; autoinflammation; pyrin; NLRP3; inflammasome; cystic fibrosis; IFN; proteasome; inflammation; infection; innate immunity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Translational Medicine (Leeds) |
Funding Information: | Funder Grant number Cystic Fibrosis Trust SRC009 |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Nov 2016 13:19 |
Last Modified: | 30 Sep 2017 20:18 |
Published Version: | https://doi.org/10.1002/path.4812 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/path.4812 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107921 |