Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis
Abstract Background Helios is important for functional and phenotype stability of regulatory T cells (Tregs). However, the role of Helios in autoimmune diseases and its regulation remains unclear. This study aimed to investigate the role of Helios+ Tregs in myasthenia gravis (MG) and glucocorticoid-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1916-1 |
| _version_ | 1819003748963319808 |
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| author | Yi Li Shumei Yang Zhibin Li Huanyu Meng Wanling Jin Huan Yang Weifan Yin |
| author_facet | Yi Li Shumei Yang Zhibin Li Huanyu Meng Wanling Jin Huan Yang Weifan Yin |
| author_sort | Yi Li |
| collection | DOAJ |
| description | Abstract Background Helios is important for functional and phenotype stability of regulatory T cells (Tregs). However, the role of Helios in autoimmune diseases and its regulation remains unclear. This study aimed to investigate the role of Helios+ Tregs in myasthenia gravis (MG) and glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand (GITRL) in the modulation of Helios. Method Multicolor flow cytometry was performed to analyze Helios+ Tregs in peripheral blood from MG patients and healthy donors (HDs). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of soluble GITRL/GITR in plasma. Tregs were isolated via magnetic separation and treated with recombinant GITRL and GITR-Fc. Membrane GITRL on Tregs and expression of Helios and other markers (FOXP3, CD25, CD39, CTLA-4, PD-L1 and IL-10) involved in immunosuppressive activity were determined by flow cytometry. Result Both Helios+ Tregs and soluble GITR were decreased in generalized MG (GMG) patients (n = 14), compared with HDs (n = 14) and ocular MG (OMG) patients (n = 16). Helios+ Tregs possessed greater immunosuppressive capacity compared to Helios− Tregs. Further analysis indicates soluble GITR was negatively correlated with quantitative MG score and promoted Helios expression and enhanced function of Tregs independently of membrane GITRL. Conclusion This work demonstrates abnormal changes in Helios+ Tregs and soluble GITR in MG, as well as direct regulation of Helios by GITR in the context of Tregs. This work provides new insight into the role of GITR in the regulatory pathway of Helios and pathogenesis of MG. |
| first_indexed | 2024-12-20T23:25:56Z |
| format | Article |
| id | doaj.art-7d964fe359514bab9118620fba6be325 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-20T23:25:56Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-7d964fe359514bab9118620fba6be3252022-12-21T19:23:24ZengBMCJournal of Translational Medicine1479-58762019-05-0117111010.1186/s12967-019-1916-1Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravisYi Li0Shumei Yang1Zhibin Li2Huanyu Meng3Wanling Jin4Huan Yang5Weifan Yin6Department of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Xiangya Hospital, Central South UniversityDepartment of Neurology, Second Xiangya Hospital, Central South UniversityAbstract Background Helios is important for functional and phenotype stability of regulatory T cells (Tregs). However, the role of Helios in autoimmune diseases and its regulation remains unclear. This study aimed to investigate the role of Helios+ Tregs in myasthenia gravis (MG) and glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand (GITRL) in the modulation of Helios. Method Multicolor flow cytometry was performed to analyze Helios+ Tregs in peripheral blood from MG patients and healthy donors (HDs). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of soluble GITRL/GITR in plasma. Tregs were isolated via magnetic separation and treated with recombinant GITRL and GITR-Fc. Membrane GITRL on Tregs and expression of Helios and other markers (FOXP3, CD25, CD39, CTLA-4, PD-L1 and IL-10) involved in immunosuppressive activity were determined by flow cytometry. Result Both Helios+ Tregs and soluble GITR were decreased in generalized MG (GMG) patients (n = 14), compared with HDs (n = 14) and ocular MG (OMG) patients (n = 16). Helios+ Tregs possessed greater immunosuppressive capacity compared to Helios− Tregs. Further analysis indicates soluble GITR was negatively correlated with quantitative MG score and promoted Helios expression and enhanced function of Tregs independently of membrane GITRL. Conclusion This work demonstrates abnormal changes in Helios+ Tregs and soluble GITR in MG, as well as direct regulation of Helios by GITR in the context of Tregs. This work provides new insight into the role of GITR in the regulatory pathway of Helios and pathogenesis of MG.http://link.springer.com/article/10.1186/s12967-019-1916-1GITRLGITRHeliosMyasthenia gravisRegulatory T cells |
| spellingShingle | Yi Li Shumei Yang Zhibin Li Huanyu Meng Wanling Jin Huan Yang Weifan Yin Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis Journal of Translational Medicine GITRL GITR Helios Myasthenia gravis Regulatory T cells |
| title | Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis |
| title_full | Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis |
| title_fullStr | Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis |
| title_full_unstemmed | Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis |
| title_short | Soluble glucocorticoid-induced tumor necrosis factor receptor regulates Helios expression in myasthenia gravis |
| title_sort | soluble glucocorticoid induced tumor necrosis factor receptor regulates helios expression in myasthenia gravis |
| topic | GITRL GITR Helios Myasthenia gravis Regulatory T cells |
| url | http://link.springer.com/article/10.1186/s12967-019-1916-1 |
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