Expression and significance of α7 nicotinic acetylcholine receptor on thymic T follicular helper cells in myasthenia gravis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Meng ^1,2 , YANG Menghao ^1,2 , CUI Xinzheng ¹ , SUN Zirui ³ , SHI Chenshuo ¹ , ZHANG Zhiwen ¹ , ZHENG Lixiang ¹ ,  ZHANG Qingyong ¹

1. Myasthenia Gravis Comprehensive Diagnosis and Treatment Center, Zhengzhou University People's Hospital/Henan Provincial People's Hospital, Zhengzhou, 450003, P. R. China;
2. General Laboratory of Henan Provincial People's Hospital, Zhengzhou, 450003, P. R. China;
3. Department of Cardiac Surgery, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450003, P. R. China;

Corresponding?author：

ZHANG Qingyong, Email: qyzhang@zzu.edu.cn

Keywords：

α7 nicotinic acetylcholine receptor; myasthenia gravis; T follicular helper cells

DOI：

10.7507/1007-4848.202312018

Video：

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Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in thymic T follicular helper cells (TFH) and its significance in patients with myasthenia gravis (MG). Methods Fifteen MG patients who underwent surgical treatment at the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People’s Hospital from June 2022 to June 2023 were selected as a MG group, including 7 males and 8 females, aged 12-30 years. Twelve patients who underwent partial thymectomy to optimize surgical field exposure during cardiac surgery at Fuwai Central China Cardiovascular Hospital from June 2022 to June 2023 were selected as a control group, including 5 males and 7 females aged 20-35 years. Thymus single cell suspension was obtained by grinding the thymus tissue, and flow cytometry was used to detect the expression of α7nAChR in TFH cells. The thymus cell suspension was purified using density gradient centrifugation, followed by immunomagnetic bead separation to obtain CD4⁺T cells. CXCR5 antibody and coupled magnetic beads were added to isolate TFH cells. Real-time fluorescent polymerase chain reaction and Western blotting were performed to further investigate the expression of α7nAChR in TFH cells. Results Compared with the control group, the proportion of thymic TFH cells in the MG group was significantly increased (P<0.05), along with significantly decreased mRNA and protein expression levels of α7nAChR within these cells (P<0.01). Conclusion The findings suggest that there is a reduced expression of α7nAChR within thymic TFH cells in MG patients, leading to weakened immunosuppressive function which may indirectly contribute to disease onset and progression.

Citation： WANG Meng, YANG Menghao, CUI Xinzheng, SUN Zirui, SHI Chenshuo, ZHANG Zhiwen, ZHENG Lixiang, ZHANG Qingyong. Expression and significance of α7 nicotinic acetylcholine receptor on thymic T follicular helper cells in myasthenia gravis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(12): 1771-1776. doi: 10.7507/1007-4848.202312018 Copy

1.	Evoli A. Myasthenia gravis: new developments in research and treatment. Curr Opin Neurol, 2017, 30(5): 464-470.
2.	Alhaidar MK, Abumurad S, Soliven B, et al. Current treatment of myasthenia gravis. J Clin Med, 2022, 11(6): 1597.
3.	Chen J, Tian DC, Zhang C, et al. Incidence mortality and economic burden of myasthenia gravis in China: a nationwide population-based study. Lancet Region Health, 2020, 5: 100063.
4.	常婷, 李柱一. 中國重癥肌無力研究進展近十年回顧與展望. 中國神經免疫學和神經病學雜志, 2022, 29(5): 349-355.Chang T, Li ZY. Review and prospect of myasthenia gravis research in China in the past decade. Chin J Neuroimmunol Neurol, 2022, 29(5): 349-355.
5.	劉寶東. 《重癥肌無力外科治療中國臨床專家共識》解讀. 中國臨床新醫學, 2023, 16(6): 531-535.Liu BD. Interpretation of Chinese clinical expert consensus on surgical treatment of myasthenia gravis. Chin J Clin New Med, 2023, 16(6): 531-535.
6.	Wu N, Tüzün E, Cheng Y, et al. Central role of T follicular helper cells in myasthenia gravis. Noro Psikiyatr Ars, 2021, 58(1): 68-72.
7.	Schaerli P, Willimann K, Lang AB, et al. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med, 2000, 192(11): 1553-1562.
8.	Havenith SH, Remmerswaal EB, Idu MM, et al. CXCR5⁺CD4⁺ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity. Int Immunol, 2014, 26(3): 183-192.
9.	Yang X, Yang J, Chu Y, et al. T follicular helper cells and regulatory B cells dynamics in systemic lupus erythematosus. PLoS One, 2014, 9(2): e88441.
10.	Li Q, Liu Z, Dang E, et al. Follicular helper T cells (Tfh) and IL-21 involvement in the pathogenesis of bullous pemphigoid. PLoS One, 2013, 8(7): e68145.
11.	Romme Christensen J, B?rnsen L, Ratzer R, et al. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression. PLoS One, 2013, 8(3): e57820.
12.	秦雨涵, 侯宏衛, 胡清源. α7煙堿型乙酰膽堿受體在膽堿能抗炎通路中的作用機制及應用現狀. 中國生物化學與分子生物學報, 2022, 38(10): 1304-1310.Qin YH, Hou HW, Hu QY. Mechanism and application of α7 nicotinic acetylcholine receptor in cholinergic anti-inflammatory pathway. Chin J Biochem Mol Biol, 2022, 38(10): 1304-1310.
13.	付博, 董力, 石應康, 等. 中國人心臟瓣膜置換術后抗凝治療數據庫建設. 中國胸心血管外科臨床雜志, 2013, 20(1): 3-9.Fu B, Dong L, Shi YK, et al. To construct a database of anticoagulant therapy after heart valve replacement in Chinese patients. Chin J Clin Cardiothorac Surg, 2013, 20(1): 3-9.
14.	Vinuesa CG, Linterman MA, Goodnow CC, et al. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev, 2010, 237(1): 72-89.
15.	Yu D, Vinuesa CG. The elusive identity of T follicular helper cells. Trends Immunol, 2010, 31(10): 377-383.
16.	Yoon SO, Zhang X, Berner P, et al. IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells. J Leukoc Biol, 2009, 86(6): 1311-1318.
17.	Ma CS, Deenick EK, Batten M, et al. The origins, function, and regulation of T follicular helper cells. J Exp Med, 2012, 209(7): 1241-1253.
18.	Zhang M, Zhou Y, Guo J, et al. Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma. Exp Neurol, 2014, 254: 200-205.
19.	Saito R, Onodera H, Tago H, et al. Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients. J Neuroimmunol, 2005, 170(1-2): 172-178.
20.	Luo C, Li Y, Liu W, et al. Expansion of circulating counterparts of follicular helper T cells in patients with myasthenia gravis. J Neuroimmunol, 2013, 256(1-2): 55-61.
21.	王東巖, 楊海永, 董旭, 等. 針刺調控α7nAchR激活膽堿能抗炎通路的研究現狀. 上海針灸雜志, 2020, 39(1): 116-122.Wang DY, Yang HY, Dong X, et al. Research status of acupuncture regulating α7nAchR to activate cholinergic anti-inflammatory pathway. Shanghai J Acupunct Moxibustion, 2020, 39(1): 116-122.
22.	Chen Y, Wang JY, Zhang Y, et al. Effect of transcutaneous auricular vagus nerve stimulation on the splenic α7nAchR/JAK2/STAT3 signaling pathway in LPS-induced depressive-like behavior rats. Zhen Ci Yan Jiu, 2023, 48(9): 933-938.
23.	Yu J, Zhang RF, Mao YL. Cerebellar fastigial nucleus electrostimulation attenuates inflammation in a post-infarction rat model by activating cholinergic anti-inflammatory pathway. Neurosci Lett, 2022, 788: 136860.
24.	Botticelli E, Guerriero C, Fucile S, et al. α7 Nicotinic acetylcholine receptors may improve schwann cell regenerating potential via metabotropic signaling pathways. Cells, 2023, 12(11): 1494.

1. Evoli A. Myasthenia gravis: new developments in research and treatment. Curr Opin Neurol, 2017, 30(5): 464-470.
2. Alhaidar MK, Abumurad S, Soliven B, et al. Current treatment of myasthenia gravis. J Clin Med, 2022, 11(6): 1597.
3. Chen J, Tian DC, Zhang C, et al. Incidence mortality and economic burden of myasthenia gravis in China: a nationwide population-based study. Lancet Region Health, 2020, 5: 100063.
4. 常婷, 李柱一. 中國重癥肌無力研究進展近十年回顧與展望. 中國神經免疫學和神經病學雜志, 2022, 29(5): 349-355.Chang T, Li ZY. Review and prospect of myasthenia gravis research in China in the past decade. Chin J Neuroimmunol Neurol, 2022, 29(5): 349-355.
5. 劉寶東. 《重癥肌無力外科治療中國臨床專家共識》解讀. 中國臨床新醫學, 2023, 16(6): 531-535.Liu BD. Interpretation of Chinese clinical expert consensus on surgical treatment of myasthenia gravis. Chin J Clin New Med, 2023, 16(6): 531-535.
6. Wu N, Tüzün E, Cheng Y, et al. Central role of T follicular helper cells in myasthenia gravis. Noro Psikiyatr Ars, 2021, 58(1): 68-72.
7. Schaerli P, Willimann K, Lang AB, et al. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med, 2000, 192(11): 1553-1562.
8. Havenith SH, Remmerswaal EB, Idu MM, et al. CXCR5⁺CD4⁺ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity. Int Immunol, 2014, 26(3): 183-192.
9. Yang X, Yang J, Chu Y, et al. T follicular helper cells and regulatory B cells dynamics in systemic lupus erythematosus. PLoS One, 2014, 9(2): e88441.
10. Li Q, Liu Z, Dang E, et al. Follicular helper T cells (Tfh) and IL-21 involvement in the pathogenesis of bullous pemphigoid. PLoS One, 2013, 8(7): e68145.
11. Romme Christensen J, B?rnsen L, Ratzer R, et al. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression. PLoS One, 2013, 8(3): e57820.
12. 秦雨涵, 侯宏衛, 胡清源. α7煙堿型乙酰膽堿受體在膽堿能抗炎通路中的作用機制及應用現狀. 中國生物化學與分子生物學報, 2022, 38(10): 1304-1310.Qin YH, Hou HW, Hu QY. Mechanism and application of α7 nicotinic acetylcholine receptor in cholinergic anti-inflammatory pathway. Chin J Biochem Mol Biol, 2022, 38(10): 1304-1310.
13. 付博, 董力, 石應康, 等. 中國人心臟瓣膜置換術后抗凝治療數據庫建設. 中國胸心血管外科臨床雜志, 2013, 20(1): 3-9.Fu B, Dong L, Shi YK, et al. To construct a database of anticoagulant therapy after heart valve replacement in Chinese patients. Chin J Clin Cardiothorac Surg, 2013, 20(1): 3-9.
14. Vinuesa CG, Linterman MA, Goodnow CC, et al. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev, 2010, 237(1): 72-89.
15. Yu D, Vinuesa CG. The elusive identity of T follicular helper cells. Trends Immunol, 2010, 31(10): 377-383.
16. Yoon SO, Zhang X, Berner P, et al. IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells. J Leukoc Biol, 2009, 86(6): 1311-1318.
17. Ma CS, Deenick EK, Batten M, et al. The origins, function, and regulation of T follicular helper cells. J Exp Med, 2012, 209(7): 1241-1253.
18. Zhang M, Zhou Y, Guo J, et al. Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma. Exp Neurol, 2014, 254: 200-205.
19. Saito R, Onodera H, Tago H, et al. Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients. J Neuroimmunol, 2005, 170(1-2): 172-178.
20. Luo C, Li Y, Liu W, et al. Expansion of circulating counterparts of follicular helper T cells in patients with myasthenia gravis. J Neuroimmunol, 2013, 256(1-2): 55-61.
21. 王東巖, 楊海永, 董旭, 等. 針刺調控α7nAchR激活膽堿能抗炎通路的研究現狀. 上海針灸雜志, 2020, 39(1): 116-122.Wang DY, Yang HY, Dong X, et al. Research status of acupuncture regulating α7nAchR to activate cholinergic anti-inflammatory pathway. Shanghai J Acupunct Moxibustion, 2020, 39(1): 116-122.
22. Chen Y, Wang JY, Zhang Y, et al. Effect of transcutaneous auricular vagus nerve stimulation on the splenic α7nAchR/JAK2/STAT3 signaling pathway in LPS-induced depressive-like behavior rats. Zhen Ci Yan Jiu, 2023, 48(9): 933-938.
23. Yu J, Zhang RF, Mao YL. Cerebellar fastigial nucleus electrostimulation attenuates inflammation in a post-infarction rat model by activating cholinergic anti-inflammatory pathway. Neurosci Lett, 2022, 788: 136860.
24. Botticelli E, Guerriero C, Fucile S, et al. α7 Nicotinic acetylcholine receptors may improve schwann cell regenerating potential via metabotropic signaling pathways. Cells, 2023, 12(11): 1494.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Expression and significance of α7 nicotinic acetylcholine receptor on thymic T follicular helper cells in myasthenia gravis

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