Cargando…

FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines

Introduction: The changes in the number and function of regulatory T cells (Tregs) are thought to play important roles in the pathogenesis of generalized myasthenia gravis (gMG). Previous studies have suggested the decrease of FoxP3(+) Treg cells in the MG development. However, there is no study on...

Descripción completa

Detalles Bibliográficos
Autores principales: Meng, Huanyu, Zheng, Shuyu, Zhou, Qinming, Gao, Yining, Ni, You, Liang, Huafeng, Chen, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718513/
https://www.ncbi.nlm.nih.gov/pubmed/34975721
http://dx.doi.org/10.3389/fneur.2021.755356
_version_ 1784624744207745024
author Meng, Huanyu
Zheng, Shuyu
Zhou, Qinming
Gao, Yining
Ni, You
Liang, Huafeng
Chen, Sheng
author_facet Meng, Huanyu
Zheng, Shuyu
Zhou, Qinming
Gao, Yining
Ni, You
Liang, Huafeng
Chen, Sheng
author_sort Meng, Huanyu
collection PubMed
description Introduction: The changes in the number and function of regulatory T cells (Tregs) are thought to play important roles in the pathogenesis of generalized myasthenia gravis (gMG). Previous studies have suggested the decrease of FoxP3(+) Treg cells in the MG development. However, there is no study on the pathophysiological mechanism of FoxP3(−)Treg, especially Tr1 cells, in gMG patients. Therefore, this study was conducted to reveal the effect of Tr1 cells to the pathophysiology of gMG. Methods: Thirteen patients with gMG and twelve healthy volunteers were enrolled in this study. The titer of anti-AChR Ab was measured by ELISA. The separated PBMCs were labeled for CD4, CD25, CD49b, LAG3 and FoxP3. The CD4(+) T cell count, FoxP3(+) Treg to CD4(+) T cell ratio and Tr1 cell to CD4(+) T cell ratio were measured by flow cytometry. Based on the FoxP3(+) Treg and Tr1 cell to CD4(+) T cell ratios, the patients' Tr1 cell to FoxP3(+) Treg ratios were calculated. The IL-6, IL-7, IL-10, TGF-β and IFN-γ concentration in the serum of MG patients and normal controls (NCs) were measured via ELISA. Results: We found a significantly positive correlation between the Tr1 cell/CD4(+) T cell ratio and the anti-AChR Ab (r = 0.6889 ± 0.4414, p = 0.0401). Although there were no significant differences in the relationship between FoxP3(+) Treg cells and anti-AChR Ab, a positive correlation between the Tr1 cell/FoxP3(+) Treg cell ratio and the anti-AChR Ab (r = 0.7110 ± 0.4227, p = 0.0318) was observed. In addition, the Tr1 cell/CD4(+) T cell ratio but not the proportion of FoxP3(+) Tregs was positively correlated with IL-10 (p = 0.048). These results suggested that in the process of the immunomodulatory effect of Tr1 cells in patients with gMG, IL-10 and other cytokines may be involved, but the specific mechanism needs further study. Conclusion: This is the first study of the immunoregulatory mechanism of Tr1 cells in gMG. We conducted this study to elucidate the significance of Tr1 cells in the pathogenesis of MG. We believe that in patients with gMG, Tr1 cells may play an immunomodulatory role in counteracting AChR-related autoimmune responses. In this process, IL-10 and other immunomodulatory cytokines may be involved.
format Online
Article
Text
id pubmed-8718513
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87185132022-01-01 FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines Meng, Huanyu Zheng, Shuyu Zhou, Qinming Gao, Yining Ni, You Liang, Huafeng Chen, Sheng Front Neurol Neurology Introduction: The changes in the number and function of regulatory T cells (Tregs) are thought to play important roles in the pathogenesis of generalized myasthenia gravis (gMG). Previous studies have suggested the decrease of FoxP3(+) Treg cells in the MG development. However, there is no study on the pathophysiological mechanism of FoxP3(−)Treg, especially Tr1 cells, in gMG patients. Therefore, this study was conducted to reveal the effect of Tr1 cells to the pathophysiology of gMG. Methods: Thirteen patients with gMG and twelve healthy volunteers were enrolled in this study. The titer of anti-AChR Ab was measured by ELISA. The separated PBMCs were labeled for CD4, CD25, CD49b, LAG3 and FoxP3. The CD4(+) T cell count, FoxP3(+) Treg to CD4(+) T cell ratio and Tr1 cell to CD4(+) T cell ratio were measured by flow cytometry. Based on the FoxP3(+) Treg and Tr1 cell to CD4(+) T cell ratios, the patients' Tr1 cell to FoxP3(+) Treg ratios were calculated. The IL-6, IL-7, IL-10, TGF-β and IFN-γ concentration in the serum of MG patients and normal controls (NCs) were measured via ELISA. Results: We found a significantly positive correlation between the Tr1 cell/CD4(+) T cell ratio and the anti-AChR Ab (r = 0.6889 ± 0.4414, p = 0.0401). Although there were no significant differences in the relationship between FoxP3(+) Treg cells and anti-AChR Ab, a positive correlation between the Tr1 cell/FoxP3(+) Treg cell ratio and the anti-AChR Ab (r = 0.7110 ± 0.4227, p = 0.0318) was observed. In addition, the Tr1 cell/CD4(+) T cell ratio but not the proportion of FoxP3(+) Tregs was positively correlated with IL-10 (p = 0.048). These results suggested that in the process of the immunomodulatory effect of Tr1 cells in patients with gMG, IL-10 and other cytokines may be involved, but the specific mechanism needs further study. Conclusion: This is the first study of the immunoregulatory mechanism of Tr1 cells in gMG. We conducted this study to elucidate the significance of Tr1 cells in the pathogenesis of MG. We believe that in patients with gMG, Tr1 cells may play an immunomodulatory role in counteracting AChR-related autoimmune responses. In this process, IL-10 and other immunomodulatory cytokines may be involved. Frontiers Media S.A. 2021-12-17 /pmc/articles/PMC8718513/ /pubmed/34975721 http://dx.doi.org/10.3389/fneur.2021.755356 Text en Copyright © 2021 Meng, Zheng, Zhou, Gao, Ni, Liang and Chen. https://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
Meng, Huanyu
Zheng, Shuyu
Zhou, Qinming
Gao, Yining
Ni, You
Liang, Huafeng
Chen, Sheng
FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title_full FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title_fullStr FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title_full_unstemmed FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title_short FoxP3(−) Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines
title_sort foxp3(−) tr1 cell in generalized myasthenia gravis and its relationship with the anti-achr antibody and immunomodulatory cytokines
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718513/
https://www.ncbi.nlm.nih.gov/pubmed/34975721
http://dx.doi.org/10.3389/fneur.2021.755356
work_keys_str_mv AT menghuanyu foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT zhengshuyu foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT zhouqinming foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT gaoyining foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT niyou foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT lianghuafeng foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines
AT chensheng foxp3tr1cellingeneralizedmyastheniagravisanditsrelationshipwiththeantiachrantibodyandimmunomodulatorycytokines