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Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that in...

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Autores principales: Lee, Ahreum, Yoo, Duck Kyun, Lee, Yonghee, Jeon, Sumin, Jung, Suhan, Noh, Jinsung, Ju, Soyeon, Hwang, Siwon, Kim, Hong Hee, Kwon, Sunghoon, Chung, Junho, Choi, Youngnim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Association of Immunologists 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568913/
https://www.ncbi.nlm.nih.gov/pubmed/34796038
http://dx.doi.org/10.4110/in.2021.21.e34
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author Lee, Ahreum
Yoo, Duck Kyun
Lee, Yonghee
Jeon, Sumin
Jung, Suhan
Noh, Jinsung
Ju, Soyeon
Hwang, Siwon
Kim, Hong Hee
Kwon, Sunghoon
Chung, Junho
Choi, Youngnim
author_facet Lee, Ahreum
Yoo, Duck Kyun
Lee, Yonghee
Jeon, Sumin
Jung, Suhan
Noh, Jinsung
Ju, Soyeon
Hwang, Siwon
Kim, Hong Hee
Kwon, Sunghoon
Chung, Junho
Choi, Youngnim
author_sort Lee, Ahreum
collection PubMed
description Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.
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spelling pubmed-85689132021-11-17 Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice Lee, Ahreum Yoo, Duck Kyun Lee, Yonghee Jeon, Sumin Jung, Suhan Noh, Jinsung Ju, Soyeon Hwang, Siwon Kim, Hong Hee Kwon, Sunghoon Chung, Junho Choi, Youngnim Immune Netw Original Article Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production. The Korean Association of Immunologists 2021-10-22 /pmc/articles/PMC8568913/ /pubmed/34796038 http://dx.doi.org/10.4110/in.2021.21.e34 Text en Copyright © 2021. The Korean Association of Immunologists https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Ahreum
Yoo, Duck Kyun
Lee, Yonghee
Jeon, Sumin
Jung, Suhan
Noh, Jinsung
Ju, Soyeon
Hwang, Siwon
Kim, Hong Hee
Kwon, Sunghoon
Chung, Junho
Choi, Youngnim
Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title_full Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title_fullStr Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title_full_unstemmed Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title_short Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
title_sort induction of anti-aquaporin 5 autoantibody production by immunization with a peptide derived from the aquaporin of prevotella melaninogenica leads to reduced salivary flow in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568913/
https://www.ncbi.nlm.nih.gov/pubmed/34796038
http://dx.doi.org/10.4110/in.2021.21.e34
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