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Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829512/ https://www.ncbi.nlm.nih.gov/pubmed/33505961 http://dx.doi.org/10.3389/fcell.2020.597769 |
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author | Xu, Kai Chen, Sen Xie, Le Qiu, Yue Bai, Xue Liu, Xiao-Zhou Zhang, Hui-Min Wang, Xiao-Hui Jin, Yuan Sun, Yu Kong, Wei-Jia |
author_facet | Xu, Kai Chen, Sen Xie, Le Qiu, Yue Bai, Xue Liu, Xiao-Zhou Zhang, Hui-Min Wang, Xiao-Hui Jin, Yuan Sun, Yu Kong, Wei-Jia |
author_sort | Xu, Kai |
collection | PubMed |
description | The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice. |
format | Online Article Text |
id | pubmed-7829512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78295122021-01-26 Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models Xu, Kai Chen, Sen Xie, Le Qiu, Yue Bai, Xue Liu, Xiao-Zhou Zhang, Hui-Min Wang, Xiao-Hui Jin, Yuan Sun, Yu Kong, Wei-Jia Front Cell Dev Biol Cell and Developmental Biology The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7829512/ /pubmed/33505961 http://dx.doi.org/10.3389/fcell.2020.597769 Text en Copyright © 2021 Xu, Chen, Xie, Qiu, Bai, Liu, Zhang, Wang, Jin, Sun and Kong. 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 | Cell and Developmental Biology Xu, Kai Chen, Sen Xie, Le Qiu, Yue Bai, Xue Liu, Xiao-Zhou Zhang, Hui-Min Wang, Xiao-Hui Jin, Yuan Sun, Yu Kong, Wei-Jia Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title | Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title_full | Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title_fullStr | Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title_full_unstemmed | Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title_short | Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models |
title_sort | local macrophage-related immune response is involved in cochlear epithelial damage in distinct gjb2-related hereditary deafness models |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829512/ https://www.ncbi.nlm.nih.gov/pubmed/33505961 http://dx.doi.org/10.3389/fcell.2020.597769 |
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