Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (10): 1-8.doi: 10.6040/j.issn.1671-7554.0.2023.0196

• Preclinical Medicine •     Next Articles

Immunomodulatory effects of lipopolysaccharide-induced Treg imbalance on experimental autoimmune myasthenia gravis

LI Liangkang1, SI Weiyue1, WU Xingyuan2, ZHOU Yang2, WEI Shuli1, DONG Jing2, LI Xiaoli1,2, DUAN Ruisheng1,2   

  1. 1. Department of Neurology, Shandong Provincial Qianfoshan Hospital of Shandong University, Jinan 250014, Shandong, China;
    2. Department of Neurology, The First Affiliated Hospital of Shandong First Medical University &
    Shandong Provincial Qianfoshan Hospital, Shandong Institute of Neuroimmunology, Shandong Provincial Medicine and Health Key Laboratory of Neuroimmunology, Jinan 250014, Shandong, China
  • Published:2023-11-08

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Abstract: Objective To investigate the changes and functional characteristics of immune cells in experimental autoimmune myasthenia gravis(EAMG)complicated with acute infection. Methods Female Lewis rats aged 6-8 weeks were immunized with R97-116 peptide of rat acetylcholine receptor alpha subunit. Lipopolysaccharide(LPS)was injected intraperitoneally to induce acute infection(LPS group), and PBS was injected intraperitoneally to set controls(PBS group). Clinical scores and body weight were recorded. Flow cytometry was used to detect the frequencies of Th1, Th17 and Treg cells from lymphoid organs and peripheral circulation, and follicular helper T(Tfh)cells, dendritic cells(DCs)and germinal center B(GCB)cells in the spleen. Peanut agglutinin(PNA), CD4 and Foxp3 levels in the spleen were detected with immunofluorescence. The levels of anti-R97-116 IgG antibody and its subclasses in serum were analyzed with ELISA. Results Compared with the PBS group, the LPS group had aggravated clinical symptoms and lower body weight. The frequency of Treg(CD4+CD25+)in the spleen was decreased(P=0.016), and the Foxp3 expression in the spleen was reduced. In addition, the PNA in the spleen of the LPS group was increased and clustered, and the expression of MHC-Ⅱ(P=0.002)and secretion of IL-6(P=0.017)of GCB cells were increased. The mean fluorescence intensity(MFI)of DC subclass expressing CD80 was increased but not statistically significant(P=0.057). The level of protective antibody IgG1 in peripheral blood was decreased in LPS group(P=0.005), the level of pathogenic antibody IgG2b did not change, and IgG1/IgG2b was down-regulated(P=0.018). Conclusion LPS may reduce the frequency of Treg cells and the expression of Foxp3 in the spleen, enhance the germinal center response, function of GCB cells and ability of DC co-stimulation, eventually leads to the aggravation of clinical symptoms of EAMG rats.

[1] 常婷.中国重症肌无力诊断和治疗指南(2020版)[J].中国神经免疫学和神经病学杂志,2021,28(1):1-12. CHANG Ting. China guidelines for the diagnosis and treatment of myasthenia gravis(2020 version)[J]. Chinese Journal of Neuroimmunology and Neurology, 2021, 28(1): 1-12.
[2] Gilhus NE, Romi F, Hong Y, et al. Myasthenia gravis and infectious disease [J]. Neurol, 2018, 265(6): 1251-1258.
[3] Kassardjian CD, Widdifield J, Paterson JM, et al. Serious infections in patients with myasthenia gravis: population-based cohort study [J]. Eur J Neurol, 2020, 27(4): 702-708.
[4] Su M, Jin S, Jiao K, et al. Pneumonia in myasthenia gravis: Microbial etiology and clinical management [J]. Front Cell Infect Microbiol, 2022, 12: 1016728. doi: 10.3389/fcimb.2022.1016728.
[5] Ramos-Fransi A, Rojas-Garcia R, Segovia S, et al. Myasthenia gravis: descriptive analysis of life-threatening events in a recent nationwide registry [J]. Eur J Neurol, 2015, 22(7): 1056-1061.
[6] Rodrigues CL, de Freitas HC, Lima PRO, et al. Myasthenia gravis exacerbation and myasthenic crisis associated with COVID-19: case series and literature review [J]. Neurol Sci, 2022, 43(4): 2271-2276.
[7] Villegas JA, Van Wassenhove J, Le Panse R, et al. An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor-positive myasthenia gravis patients [J]. Ann N Y Acad Sci, 2018, 1413(1): 154-162.
[8] Cao Y, Amezquita RA, Kleinstein SH, et al. Autoreactive T cells from patients with myasthenia gravis are characterized by elevated IL-17, IFN-gamma, and GM-CSF and diminished IL-10 production [J]. J Immunol, 2016, 196(5): 2075-2084.
[9] Barzago C, Lum J, Cavalcante P, et al. A novel infection- and inflammation associated molecular signature in peripheral blood of myasthenia gravis patients [J]. Immunobiology, 2016, 221(11): 1227-1236.
[10] Jin W, Yang Q, Peng Y, et al. Single-cell RNA-Seq reveals transcriptional heterogeneity and immune subtypes associated with disease activity in human myasthenia gravis [J]. Cell discovery, 2021, 7(1): 1-18.
[11] Ashida S, Ochi H, Hamatani M, et al. Immune skew of circulating follicular helper T cells associates with myasthenia gravis severity [J]. Neurol Neuroimmunol Neuroinflamm, 2021, 8(2):e945. doi:10.1212/NXI.0000000000000945.
[12] Villegas JA, Van Wassenhove J, Merrheim J, et al. Blocking interleukin-23 ameliorates neuromuscular and thymic defects inmyasthenia gravis [J]. J Neuroinflammation, 2023, 20(1): 9.
[13] Huan X, Luo S, Zhong H, et al. In-depth peripheral CD4+ T profile correlates with myasthenic crisis [J]. Ann Clin Transl Neurol, 2021, 8(4): 749-762.
[14] Wang Z,Yan Y. Immunopathogenesis in myasthenia gravis and neuromyelitis optica [J]. Front Immunol, 2017, 8: 1785. doi: 10.3389/fimmu.2017.01785.
[15] Abebe F. Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: a review of current understanding [J]. Int Rev Immunol, 2019, 38(4): 172-179.
[16] Cardona P, Cardona PJ. Regulatory T cells in mycobacterium tuberculosis infection [J]. Front Immunol, 2019,10:2139. doi:10.3389/fimmu.2019.02139.
[17] Brady J, Horie S, Laffey JG. Role of the adaptive immune response in sepsis [J]. Intensive Care Med Exp, 2020, 8(Suppl1): 20.
[18] 杨雪,李智,周宗贞. 免疫细胞在脓毒血症中的作用及机制研究进展[J].药学进展, 2020, 44(3):215-221.YANG Xue, LI Zhi, ZHOU Zongzhen. Advances in Research on the Role and Mechanism of Immune Cells in Sepsis[J]. Progress in Pharmaceutical Sciences, 2020, 44(3): 215-221.
[19] Green AM, Mattila JT, Bigbee CL, et al. CD4(+)regulatory T cells in a cynomolgus macaque model of mycobacterium tuberculosis infection [J]. J Infect Dis, 2010, 202(4): 533- 541.
[20] Bayati F, Mohammadi M, Valadi M,et al. The therapeutic potential of regulatory T cells: challenges and opportunities [J]. Front Immunol,2021,11:585819.doi:10.3389/fimmu.2020.585819.
[21] Xiao BG, Duan RS, Link H, et al. Induction of peripheral tolerance to experimental autoimmune myasthenia gravis by acetylcholine receptor-pulsed dendritic cells [J]. Cell Immunol, 2003, 223(1): 63-69.
[22] Puga I, Cols M, Barra CM, et al. B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen [J]. Nat Immunol, 2011, 13(2): 170-180.
[23] Kolar GR, Mehta D, elayo R, et al. A novel human B cell subpopulation representing the initial germinal center population to express AID [J]. Blood, 2007, 109(6): 2545-2552.
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