糖尿病对重症肌无力NK细胞亚型及功能的影响

doi:10.6040/j.issn.1671-7554.0.2022.0051

摘要/Abstract

摘要： 目的探讨重症肌无力(MG)合并糖尿病患者NK细胞亚型改变及其功能特征。方法收集2021年1月至11月期间于山东省千佛山医院神经内科住院治疗的重症肌无力患者26例,其中合并糖尿病的MG(MG+DM组)患者13例,不合并糖尿病的MG(MG组)患者13例。采用流式细胞术检测NK细胞及其亚型的比例、检测NK细胞IFN-γ和IL-17的分泌水平、检测Th1和Th17细胞比例;体外试验检测高糖处理流式分选的NK细胞其IFN-γ的分泌水平变化;最后,分析NK细胞分泌的IFN-γ与Th1和Th17细胞分化的相关性。结果 MG+DM组患者外周血CD56^bright NK比例高于MG组(P=0.022),CD56^bright NK比例与定量MG评分(QMG score)呈正相关(r_s=0.47,P=0.015);MG+DM组患者外周血IFN-γ⁺ NK细胞比例(P=0.043)和NK细胞IFN-γ平均荧光强度升高(P=0.029);体外实验中高糖组IFN-γ⁺ NK细胞比例(P=0.046)和IFN-γ平均荧光强度(P=0.011)高于对照组;IFN-γ⁺ NK细胞比例和IFN-γ的平均荧光强度与外周血Th1细胞比例(r=0.52,P=0.009;r=0.41,P=0.045)和Th17细胞比例(r=0.66,P< 0.001;r=0.60,P=0.002)呈正相关。结论糖尿病可能通过促进NK细胞分泌IFN-γ诱导Th1和Th17细胞异常分化,参与MG患者体内T细胞亚型的免疫失衡状态。

关键词: 重症肌无力, 糖尿病, 自然杀伤细胞, CD56^bright NK细胞, 干扰素-γ

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 CD56^bright NK was higher in MG+DM group than in MG group(P=0.022), and frequency of CD56^bright was positively correlated to the quantitative MG(QMG)score(r_s=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, CD56^bright NK cells, Interferon-γ

中图分类号:

R746.1

李涛,杨春林,杜通,李亨,王聪聪,李晓丽,段瑞生,张蓬. 糖尿病对重症肌无力NK细胞亚型及功能的影响[J]. 山东大学学报 (医学版), 2022, 60(5): 31-36.

LI Tao, YANG Chunlin, DU Tong, LI Heng, WANG Congcong, LI Xiaoli, DUAN Ruisheng,ZHANG Peng. Effects of diabetes mellitus on the subsets and function of NK cells in myasthenia gravis[J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 31-36.

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