Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway
Abstract Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. While neuroendocrine-immune system dysfunction plays a crucial role in the development of autoimmune diseases, its involvement in MG remains largely unexplored. Kisspeptin, a neuropeptide hormone...
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BMC
2025-06-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03486-4 |
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| author | Dan Lu Linqi Liu Wenjun Que Rui Fan Pingyang Ke Jing Dong Yaoqi Gan Fei Xiao |
| author_facet | Dan Lu Linqi Liu Wenjun Que Rui Fan Pingyang Ke Jing Dong Yaoqi Gan Fei Xiao |
| author_sort | Dan Lu |
| collection | DOAJ |
| description | Abstract Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. While neuroendocrine-immune system dysfunction plays a crucial role in the development of autoimmune diseases, its involvement in MG remains largely unexplored. Kisspeptin, a neuropeptide hormone and endogenous ligand for GPR54 receptor, has been demonstrated to regulate antitumor immunity, antiviral immunity, and several autoimmune diseases. However, the role and mechanism of kisspeptin in MG remain to be elucidated. Methods Serum kisspeptin levels were measured by ELISA in MG patients and experimental autoimmune myasthenia gravis (EAMG) rats. EAMG rats were treated with KP10 (kisspeptin analog) to evaluate its effects on body weight, clinical scores, grip strength, antibody levels, and complement deposition. Hypothalamic Kiss1 expression was assessed using Western blot and immunofluorescence. Stereotactic injection of adeno-associated virus overexpressing Kiss1 was performed to study its regulatory effects on disease progression. CD4+ T cell transfer via tail vein, Western blot, and flow cytometry were employed to investigate KP10’s modulatory effects on CD4+ T cell subsets and the NF-κB signaling pathway. Results Kisspeptin expression was significantly decreased in both MG patient sera and EAMG rat sera, with reduced hypothalamic Kiss1 expression in EAMG rats. Either hypothalamic Kiss1 overexpression or intraperitoneal KP10 administration significantly improved clinical signs in EAMG rats. Further in vivo and in vitro studies revealed that KP10 ameliorated EAMG clinical signs by modulating Th1/Th17/Treg cell balance through inhibition of NF-κB signaling pathway activation in CD4+ T cells. Conclusion This study elucidates that Kisspeptin secreted by hypothalamic participates in MG pathogenesis through the Kisspeptin-GPR54-NF-κB signaling axis by regulating CD4+ T cell subset balance, suggesting that the kisspeptin/GPR54 pathway may serve as a potential therapeutic target for MG treatment. |
| format | Article |
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| institution | OA Journals |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj-art-2bfcb8f644e54a749e403bcafc65145b2025-08-20T02:10:38ZengBMCJournal of Neuroinflammation1742-20942025-06-0122111610.1186/s12974-025-03486-4Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathwayDan Lu0Linqi Liu1Wenjun Que2Rui Fan3Pingyang Ke4Jing Dong5Yaoqi Gan6Fei Xiao7Department of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Neurology Key Laboratory of Chongqing Education Commission of China, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. While neuroendocrine-immune system dysfunction plays a crucial role in the development of autoimmune diseases, its involvement in MG remains largely unexplored. Kisspeptin, a neuropeptide hormone and endogenous ligand for GPR54 receptor, has been demonstrated to regulate antitumor immunity, antiviral immunity, and several autoimmune diseases. However, the role and mechanism of kisspeptin in MG remain to be elucidated. Methods Serum kisspeptin levels were measured by ELISA in MG patients and experimental autoimmune myasthenia gravis (EAMG) rats. EAMG rats were treated with KP10 (kisspeptin analog) to evaluate its effects on body weight, clinical scores, grip strength, antibody levels, and complement deposition. Hypothalamic Kiss1 expression was assessed using Western blot and immunofluorescence. Stereotactic injection of adeno-associated virus overexpressing Kiss1 was performed to study its regulatory effects on disease progression. CD4+ T cell transfer via tail vein, Western blot, and flow cytometry were employed to investigate KP10’s modulatory effects on CD4+ T cell subsets and the NF-κB signaling pathway. Results Kisspeptin expression was significantly decreased in both MG patient sera and EAMG rat sera, with reduced hypothalamic Kiss1 expression in EAMG rats. Either hypothalamic Kiss1 overexpression or intraperitoneal KP10 administration significantly improved clinical signs in EAMG rats. Further in vivo and in vitro studies revealed that KP10 ameliorated EAMG clinical signs by modulating Th1/Th17/Treg cell balance through inhibition of NF-κB signaling pathway activation in CD4+ T cells. Conclusion This study elucidates that Kisspeptin secreted by hypothalamic participates in MG pathogenesis through the Kisspeptin-GPR54-NF-κB signaling axis by regulating CD4+ T cell subset balance, suggesting that the kisspeptin/GPR54 pathway may serve as a potential therapeutic target for MG treatment.https://doi.org/10.1186/s12974-025-03486-4Neuroendocrine-immune systemKisspeptinGPR54NF-κBCD4+ T cellMyasthenia gravis |
| spellingShingle | Dan Lu Linqi Liu Wenjun Que Rui Fan Pingyang Ke Jing Dong Yaoqi Gan Fei Xiao Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway Journal of Neuroinflammation Neuroendocrine-immune system Kisspeptin GPR54 NF-κB CD4+ T cell Myasthenia gravis |
| title | Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway |
| title_full | Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway |
| title_fullStr | Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway |
| title_full_unstemmed | Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway |
| title_short | Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway |
| title_sort | hypothalamic kisspeptin alleviates myasthenia gravis by regulating th1 th17 treg balance through inhibition of nf κb signaling pathway |
| topic | Neuroendocrine-immune system Kisspeptin GPR54 NF-κB CD4+ T cell Myasthenia gravis |
| url | https://doi.org/10.1186/s12974-025-03486-4 |
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