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Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge

Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1β and IL-18 and indu...

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Autores principales: Yang, Chin-An, Chiang, Bor-Luen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685913/
https://www.ncbi.nlm.nih.gov/pubmed/33236284
http://dx.doi.org/10.1007/s12016-020-08825-2
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author Yang, Chin-An
Chiang, Bor-Luen
author_facet Yang, Chin-An
Chiang, Bor-Luen
author_sort Yang, Chin-An
collection PubMed
description Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1β and IL-18 and induce gasdermin D-mediated pyroptosis. Dysregulated inflammasome signaling could lead to hyperinflammation in response to environmental triggers, thus contributing to the pathogenesis of childhood autoimmune/autoinflammatory diseases. In this review, we group childhood rheumatic diseases into the autoinflammation to autoimmunity spectrum and discuss about the involvement of inflammasomes in disease mechanisms. Genetic mutations in inflammasome components cause monogenic autoinflammatory diseases, while inflammasome-related genetic variants have been implicated in polygenic childhood rheumatic diseases. We highlight the reported associations of inflammasome signaling-related genetic polymorphisms/protein levels with pediatric autoimmune disease susceptibility and disease course. Furthermore, we discuss about the use of IL-1 receptor antagonist as an adjunctive therapy in several childhood autoimmune diseases, including macrophage activation syndrome (MAS) and multisystem inflammatory syndrome in children (MIS-C) related to COVID-19. A comprehensive multi-cohort comparison on inflammasome gene expression profile in different pediatric rheumatic diseases is needed to identify patient subsets that might benefit from the adjunctive therapy of IL-1β inhibitors.
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spelling pubmed-76859132020-11-25 Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge Yang, Chin-An Chiang, Bor-Luen Clin Rev Allergy Immunol Article Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1β and IL-18 and induce gasdermin D-mediated pyroptosis. Dysregulated inflammasome signaling could lead to hyperinflammation in response to environmental triggers, thus contributing to the pathogenesis of childhood autoimmune/autoinflammatory diseases. In this review, we group childhood rheumatic diseases into the autoinflammation to autoimmunity spectrum and discuss about the involvement of inflammasomes in disease mechanisms. Genetic mutations in inflammasome components cause monogenic autoinflammatory diseases, while inflammasome-related genetic variants have been implicated in polygenic childhood rheumatic diseases. We highlight the reported associations of inflammasome signaling-related genetic polymorphisms/protein levels with pediatric autoimmune disease susceptibility and disease course. Furthermore, we discuss about the use of IL-1 receptor antagonist as an adjunctive therapy in several childhood autoimmune diseases, including macrophage activation syndrome (MAS) and multisystem inflammatory syndrome in children (MIS-C) related to COVID-19. A comprehensive multi-cohort comparison on inflammasome gene expression profile in different pediatric rheumatic diseases is needed to identify patient subsets that might benefit from the adjunctive therapy of IL-1β inhibitors. Springer US 2020-11-25 2021 /pmc/articles/PMC7685913/ /pubmed/33236284 http://dx.doi.org/10.1007/s12016-020-08825-2 Text en © Springer Science+Business Media, LLC, part of Springer Nature 2020 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Yang, Chin-An
Chiang, Bor-Luen
Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title_full Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title_fullStr Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title_full_unstemmed Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title_short Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge
title_sort inflammasomes and childhood autoimmune diseases: a review of current knowledge
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685913/
https://www.ncbi.nlm.nih.gov/pubmed/33236284
http://dx.doi.org/10.1007/s12016-020-08825-2
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