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NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies
The NLRP3 inflammasome is one of the NOD-like receptor family members with the most functional characterization and acts as a key player in innate immune system, participating in several physiological processes including, among others, the modulation of the immune system response and the coordinatio...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583146/ https://www.ncbi.nlm.nih.gov/pubmed/36275641 http://dx.doi.org/10.3389/fimmu.2022.1007705 |
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author | Moltrasio, Chiara Romagnuolo, Maurizio Marzano, Angelo Valerio |
author_facet | Moltrasio, Chiara Romagnuolo, Maurizio Marzano, Angelo Valerio |
author_sort | Moltrasio, Chiara |
collection | PubMed |
description | The NLRP3 inflammasome is one of the NOD-like receptor family members with the most functional characterization and acts as a key player in innate immune system, participating in several physiological processes including, among others, the modulation of the immune system response and the coordination of host defences. Activation of the inflammasome is a crucial signaling mechanism that promotes both an acute and a chronic inflammatory response, which can accelerate the production of pro-inflammatory cytokines, mainly Interleukin (IL)-1β and IL-18, leading to an exacerbated inflammatory network. Cryopyrin associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disorder, clinically characterized by cutaneous and systemic, musculoskeletal, and central nervous system inflammation. Gain-of-function mutations in NLRP3 gene are causative of signs and inflammatory symptoms in CAPS patients, in which an abnormal activation of the NLRP3 inflammasome, resulting in an inappropriate release of IL-1β and gasdermin-D-dependent pyroptosis, has been demonstrated both in in vitro and in ex vivo studies. During recent years, two new hereditary NLRP3-related disorders have been described, deafness autosomal dominant 34 (DFN34) and keratitis fugax hereditaria (KFH), with an exclusive cochlear- and anterior eye- restricted autoinflammation, respectively, and caused by mutations in NLRP3 gene, thus expanding the clinical and genetic spectrum of NLRP3-associated autoinflammatory diseases. Several crucial mechanisms involved in the control of activation and regulation of the NLRP3 inflammasome have been identified and researchers took advantage of this to develop novel target therapies with a significant improvement of clinical signs and symptoms of NLRP3-associated diseases. This review provides a broad overview of NLRP3 inflammasome biology with particular emphasis on CAPS, whose clinical, genetic, and therapeutic aspects will be explored in depth. The latest evidence on two “new” diseases, DFN34 and KFH, caused by mutations in NLRP3 is also described. |
format | Online Article Text |
id | pubmed-9583146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95831462022-10-21 NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies Moltrasio, Chiara Romagnuolo, Maurizio Marzano, Angelo Valerio Front Immunol Immunology The NLRP3 inflammasome is one of the NOD-like receptor family members with the most functional characterization and acts as a key player in innate immune system, participating in several physiological processes including, among others, the modulation of the immune system response and the coordination of host defences. Activation of the inflammasome is a crucial signaling mechanism that promotes both an acute and a chronic inflammatory response, which can accelerate the production of pro-inflammatory cytokines, mainly Interleukin (IL)-1β and IL-18, leading to an exacerbated inflammatory network. Cryopyrin associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disorder, clinically characterized by cutaneous and systemic, musculoskeletal, and central nervous system inflammation. Gain-of-function mutations in NLRP3 gene are causative of signs and inflammatory symptoms in CAPS patients, in which an abnormal activation of the NLRP3 inflammasome, resulting in an inappropriate release of IL-1β and gasdermin-D-dependent pyroptosis, has been demonstrated both in in vitro and in ex vivo studies. During recent years, two new hereditary NLRP3-related disorders have been described, deafness autosomal dominant 34 (DFN34) and keratitis fugax hereditaria (KFH), with an exclusive cochlear- and anterior eye- restricted autoinflammation, respectively, and caused by mutations in NLRP3 gene, thus expanding the clinical and genetic spectrum of NLRP3-associated autoinflammatory diseases. Several crucial mechanisms involved in the control of activation and regulation of the NLRP3 inflammasome have been identified and researchers took advantage of this to develop novel target therapies with a significant improvement of clinical signs and symptoms of NLRP3-associated diseases. This review provides a broad overview of NLRP3 inflammasome biology with particular emphasis on CAPS, whose clinical, genetic, and therapeutic aspects will be explored in depth. The latest evidence on two “new” diseases, DFN34 and KFH, caused by mutations in NLRP3 is also described. Frontiers Media S.A. 2022-10-06 /pmc/articles/PMC9583146/ /pubmed/36275641 http://dx.doi.org/10.3389/fimmu.2022.1007705 Text en Copyright © 2022 Moltrasio, Romagnuolo and Marzano https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Moltrasio, Chiara Romagnuolo, Maurizio Marzano, Angelo Valerio NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title | NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title_full | NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title_fullStr | NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title_full_unstemmed | NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title_short | NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies |
title_sort | nlrp3 inflammasome and nlrp3-related autoinflammatory diseases: from cryopyrin function to targeted therapies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583146/ https://www.ncbi.nlm.nih.gov/pubmed/36275641 http://dx.doi.org/10.3389/fimmu.2022.1007705 |
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