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Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis
Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR(+) autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is acti...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837970/ https://www.ncbi.nlm.nih.gov/pubmed/36639663 http://dx.doi.org/10.1186/s12974-023-02691-3 |
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author | Villegas, José A. Van Wassenhove, Jérôme Merrheim, Judith Matta, Karen Hamadache, Samy Flaugère, Clémence Pothin, Pauline Truffault, Frédérique Hascoët, Sébastien Santelmo, Nicola Alifano, Marco Berrih-Aknin, Sonia le Panse, Rozen Dragin, Nadine |
author_facet | Villegas, José A. Van Wassenhove, Jérôme Merrheim, Judith Matta, Karen Hamadache, Samy Flaugère, Clémence Pothin, Pauline Truffault, Frédérique Hascoët, Sébastien Santelmo, Nicola Alifano, Marco Berrih-Aknin, Sonia le Panse, Rozen Dragin, Nadine |
author_sort | Villegas, José A. |
collection | PubMed |
description | Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR(+) autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR(+) MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02691-3. |
format | Online Article Text |
id | pubmed-9837970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98379702023-01-14 Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis Villegas, José A. Van Wassenhove, Jérôme Merrheim, Judith Matta, Karen Hamadache, Samy Flaugère, Clémence Pothin, Pauline Truffault, Frédérique Hascoët, Sébastien Santelmo, Nicola Alifano, Marco Berrih-Aknin, Sonia le Panse, Rozen Dragin, Nadine J Neuroinflammation Research Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR(+) autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR(+) MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02691-3. BioMed Central 2023-01-13 /pmc/articles/PMC9837970/ /pubmed/36639663 http://dx.doi.org/10.1186/s12974-023-02691-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Villegas, José A. Van Wassenhove, Jérôme Merrheim, Judith Matta, Karen Hamadache, Samy Flaugère, Clémence Pothin, Pauline Truffault, Frédérique Hascoët, Sébastien Santelmo, Nicola Alifano, Marco Berrih-Aknin, Sonia le Panse, Rozen Dragin, Nadine Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title | Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title_full | Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title_fullStr | Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title_full_unstemmed | Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title_short | Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
title_sort | blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837970/ https://www.ncbi.nlm.nih.gov/pubmed/36639663 http://dx.doi.org/10.1186/s12974-023-02691-3 |
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