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Genetic Hearing Loss Associated With Autoinflammation
Sensorineural hearing loss can result from dysfunction of the inner ear, auditory nerve, or auditory pathways in the central nervous system. Sensorineural hearing loss can be associated with age, exposure to ototoxic drugs or noise, or mutations in nuclear or mitochondrial genes. However, it is idio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066252/ https://www.ncbi.nlm.nih.gov/pubmed/32194497 http://dx.doi.org/10.3389/fneur.2020.00141 |
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author | Nakanishi, Hiroshi Prakash, Pragya Ito, Taku Kim, H. Jeffrey Brewer, Carmen C. Harrow, Danielle Roux, Isabelle Hosokawa, Seiji Griffith, Andrew J. |
author_facet | Nakanishi, Hiroshi Prakash, Pragya Ito, Taku Kim, H. Jeffrey Brewer, Carmen C. Harrow, Danielle Roux, Isabelle Hosokawa, Seiji Griffith, Andrew J. |
author_sort | Nakanishi, Hiroshi |
collection | PubMed |
description | Sensorineural hearing loss can result from dysfunction of the inner ear, auditory nerve, or auditory pathways in the central nervous system. Sensorineural hearing loss can be associated with age, exposure to ototoxic drugs or noise, or mutations in nuclear or mitochondrial genes. However, it is idiopathic in some patients. Although these disorders are mainly caused by dysfunction of the inner ear, little of the pathophysiology in sensorineural hearing loss is known due to inaccessibility of the living human inner ear for biopsy and pathological analysis. The inner ear has previously been thought of as an immune-privileged organ. We recently showed that a missense mutation of the NLRP3 gene is associated with autosomal-dominant sensorineural hearing loss with cochlear autoinflammation in two unrelated families. NLRP3 encodes the NLRP3 protein, a key component of the NLRP3 inflammasome that is expressed in immune cells, including monocytes and macrophages. Gain-of-function mutations of NLRP3 cause abnormal activation of the NLRP3 inflammasome leading to IL-1β secretion in a spectrum of autosomal dominant systemic autoinflammatory phenotypes termed cryopyrin-associated periodic syndromes. The affected subjects of our two families demonstrated atypical phenotypes compared with those reported for subjects with cryopyrin-associated periodic syndromes. These observations led us to test the hypothesis that macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The inflammasome can indeed be activated in macrophage/monocyte-like cells of the mouse cochlea, with secretion of IL-1β. The macrophage/monocyte-like cells in the cochlea were also found to be associated with hearing loss in a Slc26a4-insufficient mouse model of human deafness. This review addresses our understanding of genetic hearing loss mediated by autoinflammation and macrophage/monocyte-like cells in the cochlea. |
format | Online Article Text |
id | pubmed-7066252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70662522020-03-19 Genetic Hearing Loss Associated With Autoinflammation Nakanishi, Hiroshi Prakash, Pragya Ito, Taku Kim, H. Jeffrey Brewer, Carmen C. Harrow, Danielle Roux, Isabelle Hosokawa, Seiji Griffith, Andrew J. Front Neurol Neurology Sensorineural hearing loss can result from dysfunction of the inner ear, auditory nerve, or auditory pathways in the central nervous system. Sensorineural hearing loss can be associated with age, exposure to ototoxic drugs or noise, or mutations in nuclear or mitochondrial genes. However, it is idiopathic in some patients. Although these disorders are mainly caused by dysfunction of the inner ear, little of the pathophysiology in sensorineural hearing loss is known due to inaccessibility of the living human inner ear for biopsy and pathological analysis. The inner ear has previously been thought of as an immune-privileged organ. We recently showed that a missense mutation of the NLRP3 gene is associated with autosomal-dominant sensorineural hearing loss with cochlear autoinflammation in two unrelated families. NLRP3 encodes the NLRP3 protein, a key component of the NLRP3 inflammasome that is expressed in immune cells, including monocytes and macrophages. Gain-of-function mutations of NLRP3 cause abnormal activation of the NLRP3 inflammasome leading to IL-1β secretion in a spectrum of autosomal dominant systemic autoinflammatory phenotypes termed cryopyrin-associated periodic syndromes. The affected subjects of our two families demonstrated atypical phenotypes compared with those reported for subjects with cryopyrin-associated periodic syndromes. These observations led us to test the hypothesis that macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The inflammasome can indeed be activated in macrophage/monocyte-like cells of the mouse cochlea, with secretion of IL-1β. The macrophage/monocyte-like cells in the cochlea were also found to be associated with hearing loss in a Slc26a4-insufficient mouse model of human deafness. This review addresses our understanding of genetic hearing loss mediated by autoinflammation and macrophage/monocyte-like cells in the cochlea. Frontiers Media S.A. 2020-03-05 /pmc/articles/PMC7066252/ /pubmed/32194497 http://dx.doi.org/10.3389/fneur.2020.00141 Text en Copyright © 2020 Nakanishi, Prakash, Ito, Kim, Brewer, Harrow, Roux, Hosokawa and Griffith. http://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 | Neurology Nakanishi, Hiroshi Prakash, Pragya Ito, Taku Kim, H. Jeffrey Brewer, Carmen C. Harrow, Danielle Roux, Isabelle Hosokawa, Seiji Griffith, Andrew J. Genetic Hearing Loss Associated With Autoinflammation |
title | Genetic Hearing Loss Associated With Autoinflammation |
title_full | Genetic Hearing Loss Associated With Autoinflammation |
title_fullStr | Genetic Hearing Loss Associated With Autoinflammation |
title_full_unstemmed | Genetic Hearing Loss Associated With Autoinflammation |
title_short | Genetic Hearing Loss Associated With Autoinflammation |
title_sort | genetic hearing loss associated with autoinflammation |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066252/ https://www.ncbi.nlm.nih.gov/pubmed/32194497 http://dx.doi.org/10.3389/fneur.2020.00141 |
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