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Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models

Graves’ hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves’ hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance b...

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Autores principales: Luo, Yuqian, Yoshihara, Aya, Oda, Kenzaburo, Ishido, Yuko, Suzuki, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107990/
https://www.ncbi.nlm.nih.gov/pubmed/27895620
http://dx.doi.org/10.3389/fendo.2016.00144
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author Luo, Yuqian
Yoshihara, Aya
Oda, Kenzaburo
Ishido, Yuko
Suzuki, Koichi
author_facet Luo, Yuqian
Yoshihara, Aya
Oda, Kenzaburo
Ishido, Yuko
Suzuki, Koichi
author_sort Luo, Yuqian
collection PubMed
description Graves’ hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves’ hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). “Shimojo’s model” was the first successful Graves’ animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice. This model highlights the importance of coincident MHC class II expression on TSHR-expressing cells in the development of Graves’ hyperthyroidism. These data are also in agreement with the observation that Graves’ thyrocytes often aberrantly express MHC class II antigens via mechanisms that remain unclear. Our group demonstrated that cytosolic self-genomic DNA fragments derived from sterile injured cells can induce aberrant MHC class II expression and production of multiple inflammatory cytokines and chemokines in thyrocytes in vitro, suggesting that severe cell injury may initiate immune responses in a way that is relevant to thyroid autoimmunity mediated by cytosolic DNA signaling. Furthermore, more recent successful Graves’ animal models were primarily established by immunizing mice with TSHR-expressing plasmids or adenovirus. In these models, double-stranded DNA vaccine contents presumably exert similar immune-activating effect in cells at inoculation sites and thus might pave the way toward successful Graves’ animal models. This review focuses on evidence suggesting that cell injury-derived self-DNA fragments could act as Graves’ disease triggers.
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spelling pubmed-51079902016-11-28 Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models Luo, Yuqian Yoshihara, Aya Oda, Kenzaburo Ishido, Yuko Suzuki, Koichi Front Endocrinol (Lausanne) Endocrinology Graves’ hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves’ hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). “Shimojo’s model” was the first successful Graves’ animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice. This model highlights the importance of coincident MHC class II expression on TSHR-expressing cells in the development of Graves’ hyperthyroidism. These data are also in agreement with the observation that Graves’ thyrocytes often aberrantly express MHC class II antigens via mechanisms that remain unclear. Our group demonstrated that cytosolic self-genomic DNA fragments derived from sterile injured cells can induce aberrant MHC class II expression and production of multiple inflammatory cytokines and chemokines in thyrocytes in vitro, suggesting that severe cell injury may initiate immune responses in a way that is relevant to thyroid autoimmunity mediated by cytosolic DNA signaling. Furthermore, more recent successful Graves’ animal models were primarily established by immunizing mice with TSHR-expressing plasmids or adenovirus. In these models, double-stranded DNA vaccine contents presumably exert similar immune-activating effect in cells at inoculation sites and thus might pave the way toward successful Graves’ animal models. This review focuses on evidence suggesting that cell injury-derived self-DNA fragments could act as Graves’ disease triggers. Frontiers Media S.A. 2016-11-14 /pmc/articles/PMC5107990/ /pubmed/27895620 http://dx.doi.org/10.3389/fendo.2016.00144 Text en Copyright © 2016 Luo, Yoshihara, Oda, Ishido and Suzuki. 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) or licensor 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 Endocrinology
Luo, Yuqian
Yoshihara, Aya
Oda, Kenzaburo
Ishido, Yuko
Suzuki, Koichi
Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title_full Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title_fullStr Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title_full_unstemmed Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title_short Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
title_sort excessive cytosolic dna fragments as a potential trigger of graves’ disease: an encrypted message sent by animal models
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107990/
https://www.ncbi.nlm.nih.gov/pubmed/27895620
http://dx.doi.org/10.3389/fendo.2016.00144
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