Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (5): 31-36.doi: 10.6040/j.issn.1671-7554.0.2022.0051

Previous Articles     Next Articles

Effects of diabetes mellitus on the subsets and function of NK cells in myasthenia gravis

LI Tao1, YANG Chunlin2, DU Tong2, LI Heng2, WANG Congcong2, LI Xiaoli2, DUAN Ruisheng1, 2,ZHANG Peng1, 2   

  1. 1. Department of Neurology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, 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 Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan 250014, Shandong, China
  • Published:2022-06-01

PDF (PC)

266

Abstract: Objective To explore the changes and functional characteristics of NK cells subtypes in myasthenia gravis(MG)patients with diabetes mellitus. Methods The clinical data of 26 MG patients treated during Jan. 2021 and Dec. 2021 were collected, including 13 MG patients with diabetes mellitus(MG+DM group)and 13 MG patients without diabetes mellitus(MG group). The frequency of NK cells and their subtypes, expressions of IFN-γ and IL-17 in NK cells, and ratio of Th1 and Th17 cells were detected with flow cytometry. In in vitro experiment, the expressions of IFN-γ in NK cells cultured with high glucose were detected with flow cytometry. Finally, the correlation of IFN-γ secreted by NK cells with the frequency of Th1 and Th17 cells was analyzed. Results The frequency of CD56bright NK was higher in MG+DM group than in MG group(P=0.022), and frequency of CD56bright was positively correlated to the quantitative MG(QMG)score(rs=0.47, P=0.015). The frequency of IFN-γ+ NK cells(P=0.043)and mean fluorescence intensity(MFI)of IFN-γ in IFN-γ+ NK cells(P= 0.029)were increased in the MG+DM group. The frequency of IFN-γ+ NK cells(P=0.046)and MFI of IFN-γ(P=0.011)were increased in high-glucose environment than in the control. The frequency of IFN-γ+ NK cells and MFI of IFN-γ in IFN-γ+ NK cells were positively correlated with the frequency of Th1 cells(r=0.52, P=0.009; r=0.41, P=0.045)and Th17 cells(r=0.66, P<0.001; r=0.60, P=0.002). Conclusion Diabetes mellitus may induce abnormal differentiation of Th1 and Th17 cells by promoting NK cells’ secretion of IFN-γ in MG patients.

Key words: Myasthenia gravis, Diabetes mellitus, Natural killer cell, CD56bright NK cells, Interferon-γ

CLC Number: 

  • R746.1
[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.
[2] American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020 [J]. Diabetes Care, 2020, 43(Suppl 1): S14-S31.
[3] Farmaki P, Damaskos C, Garmpis N, et al. Complications of the type 2 diabetes mellitus [J]. Curr Cardiol Rev, 2020, 16(4): 249-251.
[4] Daryabor G, Atashzar MR, Kabelitz D, et al. The effects of type 2 diabetes mellitus on organ metabolism and the immune system [J]. Front Immunol, 2020, 11: 1582. doi:10.3389/fimmu.2020. 01582.
[5] Jiang MY, Hwang JC, Feng IJ. Impact of diabetes mellitus on the risk of end-stage renal disease in patients with systemic lupus erythematosus [J]. Sci Rep, 2018, 8(1): 6008.
[6] Rehling T, Bjorkman AD, Andersen MB, et al. Diabetes is associated with musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis [J]. J Diabetes Res, 2019, 2019: 6324348. doi: 10.1155/2019/6324348.
[7] Van Dyken P, Lacoste B. Impact of metabolic syndrome on neuroinflammation and the blood-brain barrier [J]. Front Neurosci, 2018, 12: 930. doi:10.3389/fnins.2018.00930.
[8] Roma S, Carpen L, Raveane A, et al. The dual role of innate lymphoid and natural killer cells in cancer. from phenotype to single-cell transcriptomics, functions and clinical uses [J]. Cancers(Basel), 2021, 13(20):5042.
[9] Guo Y, Patil NK, Luan L, et al. The biology of natural killer cells during sepsis [J]. Immunology, 2018, 153(2): 190-202.
[10] Kucuksezer UC, Aktas Cetin E, Esen F, et al. The role of natural killer cells in autoimmune diseases [J]. Front Immunol, 2021, 12: 622306. doi:10.3389/fimmu.2021.622306.
[11] Gianchecchi E, Delfino DV, Fierabracci A. NK cells in autoimmune diseases: linking innate and adaptive immune responses [J]. Autoimmun Rev, 2018, 17(2): 142-154.
[12] Liu RT, Li W, Guo D, et al. Natural killer cells promote the differentiation of follicular helper T cells instead of inducing apoptosis in myasthenia gravis [J]. Int Immunopharmacol, 2021,98:107880.doi:10.1016/j.intimp.2021.107880.
[13] Hashemi E, Malarkannan S. Tissue-resident NK cells: development, maturation, and clinical relevance [J]. Cancers(Basel), 2020, 12(6): 1553.
[14] Schepis D, Gunnarsson I, Eloranta ML, et al. Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus [J]. Immunology, 2009, 126(1): 140-146.
[15] Ming B, Wu T, Cai S, et al. The increased ratio of blood CD56(bright)NK to CD56(dim)NK is a distinguishing feature of primary sjogrens syndrome [J]. J Immunol Res, 2020, 2020: 7523914. doi:10.1155/2020/7523914.
[16] Henriques A, Teixeira L, Ines L, et al. NK cells dysfunction in systemic lupus erythematosus: relation to disease activity [J]. Clin Rheumatol, 2013, 32(6): 805-813.
[17] Laroni A, Armentani E, Kerlero de Rosbo N, et al. Dysregulation of regulatory CD56(bright)NK cells/T cells interactions in multiple sclerosis [J]. J Autoimmun, 2016, 72: 8-18. doi:10.1016/j.jaut.201604.003.
[18] Billiau A, Matthys P. Interferon-gamma: a historical perspective [J]. Cytokine Growth Factor Rev, 2009, 20(2): 97-113.
[19] Lazear HM, Nice TJ, Diamond MS. Interferon-lambda: immune functions at barrier surfaces and beyond [J]. Immunity, 2015, 43(1): 15-28.
[20] Dungan LS, Mcguinness NC, Boon L, et al. Innate IFN-gamma promotes development of experimental autoimmune encephalomyelitis: a role for NK cells and M1 macrophages [J]. Eur J Immunol, 2014, 44(10): 2903-2917.
[21] Shi FD, Wang HB, Li H, et al. Natural killer cells determine the outcome of B cell-mediated autoimmunity [J]. Nat Immunol, 2000, 1(3): 245-251.
[22] Morandi B, Bougras G, Muller WA, et al. NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-gamma secretion [J]. Eur J Immunol, 2006, 36(9): 2394-2400.
[23] Wang Z, Yan Y. Immunopathogenesis in myasthenia gravis and neuromyelitis optica [J]. Front Immunol, 2017, 8: 1785. doi:10.3389/fimmu.2017.01785.
[24] Prattichizzo F, De Nigris V, Spiga R, et al. Inflammageing and metaflammation: the yin and yang of type 2 diabetes [J]. Ageing Res Rev, 2018, 41: 1-17. doi:10.1016/j.arr.2017.10.003
[25] Han XQ, Gong ZJ, Xu SQ, et al. Advanced glycation end products promote differentiation of CD4(+)T helper cells toward pro-inflammatory response [J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(1): 10-17.
[1] SUN Lina, DU Xiaoxiao, ZHANG Hongjuan, MENG Jinlai. Human leukocyte antigen-G promotes trophoblast invasion by regulating decidual natural killer cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(6): 41-45.
[2] LI Honghao, YU Jing, CHEN Yali, GUO Shougang. Evaluation of CD4+CD25+FoxP3+ regulatory T cells and FoxP3 mRNA expression in 20 NMOSD patients [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 50-54.
[3] LYU Li, JIANG Lu, CHEN Shihong, ZHUANG Xianghua, SONG Yuwen, WANG Dianhui, AN Wenjuan, LI Qian, PAN Zhe. Related factors of osteoporosis in 210 postmenopausal women with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 19-25.
[4] ZHENG Fengjie, SONG Yuwen, SUN Aili, PAN Zhe, WANG Dianhui, LOU Nengjun, LYU Li, ZHUANG Xianghua, CHEN Shihong. Correlation between diabetic peripheral neuropathy and sarcopenia [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 38-44.
[5] LIU Ping, SONG Yuwen, WANG Ping, TIAN Guangwei, ZHENG Fengjie, LYU Li, DU Jiaojiao, ZHANG Jing, ZHUANG Xianghua, CHEN Shihong. Correlation between vitamin D deficiency and depression in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 51-56.
[6] XIAO Yang, TAO Yu, WANG Fangyi, LIANG Yuxiu, ZHANG Jin, JI Xiaokang, WANG Zhiping. Association between PM2.5 and PM10 exposure with gestational diabetes mellitus in certain areas of Shandong Province [J]. Journal of Shandong University (Health Sciences), 2021, 59(12): 101-109.
[7] GAO Xiaoli, ZHOU Xueying, ZHOU Shengnian. Hepatolenticular degeneration with myasthenia gravis: a case report [J]. Journal of Shandong University (Health Sciences), 2021, 59(1): 88-90.
[8] WANG Yuyu, GAO Li, CHEN Shaohua. Association between cognitive impairment and thyroid function after acute ischemic stroke in 94 patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 56-61.
[9] TANG Bo, SHAO Jing, CUI Jing, SUN Jianping. A mechanism study on the association of type 2 diabetes and high-density lipoprotein [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 99-106.
[10] JIN Haiyan, ZHANG Yan, MA Xiaoli, HAN Yu, ZHAO Huichen, LIU Yuantao, ZHANG Yuchao. Expressions of miR-122 and miR-33a in patients with type 2 diabetes complicated with coronary artery disease [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 94-98.
[11] ZHOU Xiaoqing, LI Jing, ZHAO Lei, TANG Wei, YANG Xi, WANG Hong. Natural killer cells regulate Th17/Treg cell immune response through modulating the function of dendritic cells during chlamydial lung infection [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 15-19.
[12] TIAN Zhongyan, LI Yuqian, LIU Xiaotian, SHI Yuanyuan, ZHANG Haiqing, ZHANG Xia, QIAN Xinling, YIN Lei, ZHAO Jingzhi, WANG Chongjian. Relationship between PSMD6 gene rs831571 locus polymorphism and the susceptibility of T2DM: a case-control study [J]. Journal of Shandong University (Health Sciences), 2018, 56(7): 51-56.
[13] MA Xiao, WANG Shue, CAI Yunxi, LIU Houfu, HE Tianyu, ZHAO Changfeng. Hypoglycemic effects of whole rye flour on experimental diabetic mice [J]. Journal of Shandong University (Health Sciences), 2018, 56(2): 88-92.
[14] CHEN Pan, JIANG Chunxia, LEI Yi. Correlation between peripheral Syntaxin 8 expression and chronic inflammation and glucose-lipid metabolism in type 2 diabetes mellitus patients [J]. Journal of Shandong University (Health Sciences), 2018, 56(12): 26-32.
[15] LAN Jing, LI Dong, SHI Qing, LIU Zilin, ZHOU Panpan, JU Xiuli. Umbilical cord blood NK cells improved liver injury in sub-acute aging rats [J]. Journal of Shandong University (Health Sciences), 2018, 56(10): 64-71.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[2] JIANG Bao-dong,MA Xiang-xing,WANG Qing,WANG Qian,FENG Xiao-yuan,LI Ke,YU Fu-hua. Imaging parameters of multislice spiral CT venography in cerebral veins[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1084 -1086 .
[3] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[4] SHAO Haigang, WANG Xuan, WANG Qing. Anatomy of the root canal system of mandibular first premolar in population of Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 85 -89 .
[5] HUANG Fei,WANG Huaijing,XING Yi,GAO Wei,LI Yonggang,XING Ziying,LI Zhenzhong. Protective effects of NGF and GM1 on primary sensory neurons in SD rat with sciatic nerve injury[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(4): 332 -335 .
[6] DING Ling1,2, GONG Huiping1, DU Yimeng1, WANG Xin1, ZHANG Yan3, WANG Xuping2, LU Qinghua1. Effect of SIRT3 siRNA on ICAM-1 and E-selectin expressions in HAEC stimulated by ox-LDL[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 43 -48 .
[7] LI Yu-liang,WANG Yong-zheng,WANG Xiao-hua,ZHANG Fu-jun,ZHU Li-dong,ZHANG Wang-ming,LI Zheng,LI Zhen-jia,ZHANG Kai-xian. I implantation combined with Gemcitabine in the treatment of advanced pancreatic cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 393 -396 .
[8] LI Wei,LI Dao-wei,YE Qian,GAO Shun-cui,JIANG Shu-juan.

Diagnostic value of transbronchial needle aspiration in paratracheal mediastinal lesions

[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1063 -1065 .
[9] LIU Hai-Chun, ZHANG Jian-Feng, CHEN Yuan-zhen. Bone collagen and biomechanical propertyies in the femur of osteoporosis rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(5): 42 -45 .
[10] FENG Fuli1, WEI Shuzhen2, ZHANG Yonghuan3, LI Li1, CHEN Rong1, LIRuifeng1. Relationship between high mortality and altered expression of Klotho in insulin resistance rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(6): 5 -8 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd