辅助性T细胞17调控抗N-甲基-D-天冬氨酸受体脑炎的病程。
Th17 cells regulate the progress of anti-NMDAR encephalitis.
作者信息
Zeng Chaosheng, Li Li, Chen Lin, Li Pengxiang, Chen Min, Wu Xiaowen, Chen Cong
机构信息
Department of Neurology, The Second Affiliated Hospital of Hainan Medical University Haikou 570311, Hainan, China.
出版信息
Am J Transl Res. 2022 Sep 15;14(9):6268-6276. eCollection 2022.
OBJECTIVE
To explore the mechanism of immune regulation of Th17 in anti-NMDAR encephalitis disease.
METHODS
This is a retrospective study with 83 subjects included. All subjects were admitted to the Second Affiliated Hospital of Hainan Medical University from April 2018 to May 2021, including 35 patients with anti-NMDA encephalitis in an encephalitis group, and 48 patients with non-inflammatory central neuropathy in a control group. The cerebrospinal fluid (CSF) and blood samples were collected from two groups of patients, and the changes of Th17 cell, immunophenotypic characteristics, differentiation pathways and the effect were analyzed accordingly. Peripheral blood mononuclear cells (PBMCs) from patients with anti-NMDAR encephalitis were isolated and treated with different cytokines, namely IL-1β+IL-6 group, IL-1β+IL-23 group, IL-6+IL-23 group, IL-1β+IL-23+IL-6 group and TGF-β group. After co-culture, the proportion of Th17 cells and the expression level of Th17 cell-specific transcription factor RORγt mRNA were examined.
RESULTS
Th17 cells in CSF were dramatically uplifted in the encephalitis group. In terms of cell phenotype, the percentages of CD62L and CCR7 expressions in Th17 cell phenotype were significantly increased in the encephalitis group. IL-1β, IL-6, IL-7 and IL-23 mRNA in PBMCs and IL-1β, IL-6, IL-7 and IL-23 in serum were remarkably uplifted in the encephalitis group. The mRNA levels of Th17 and Th17 cell-specific transcription factor RORγ T were the highest in the IL-1β+IL-6+IL-23 group but the lowest in the TGF-β group. Th17 in CSF of patients with poor prognosis was notably higher than that of those with good prognosis.
CONCLUSION
The proportion of Th17 cells in patients with NMDAR encephalitis and the expressions of corresponding differentiation promoting cytokines were increased, and Th17 is closely associated with patients' treatment and prognosis. Th17 cells play crucial roles in tumorigenesis and progression of anti-NMDAR encephalitis.
目的
探讨辅助性T细胞17（Th17）在抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎疾病中的免疫调节机制。
方法
本研究为回顾性研究，共纳入83例受试者。所有受试者于2018年4月至2021年5月入住海南医学院第二附属医院，其中脑炎组有35例抗NMDAR脑炎患者，对照组有48例非炎性中枢神经病变患者。采集两组患者的脑脊液（CSF）和血液样本，并分析Th17细胞的变化、免疫表型特征、分化途径及效果。分离抗NMDAR脑炎患者的外周血单个核细胞（PBMCs），并用不同细胞因子进行处理，即白细胞介素-1β（IL-1β）+白细胞介素-6（IL-6）组、IL-1β+白细胞介素-23（IL-23）组、IL-6+IL-23组、IL-1β+IL-23+IL-6组和转化生长因子-β（TGF-β）组。共培养后，检测Th17细胞比例及Th17细胞特异性转录因子维甲酸相关孤儿受体γt（RORγt）mRNA的表达水平。
结果
脑炎组CSF中的Th17细胞显著升高。在细胞表型方面，脑炎组Th17细胞表型中CD62L和CC趋化因子受体7（CCR7）表达的百分比显著增加。脑炎组PBMCs中的IL-1β、IL-6、IL-7和IL-23 mRNA以及血清中的IL-1β、IL-6、IL-7和IL-23显著升高。Th17及Th17细胞特异性转录因子RORγT的mRNA水平在IL-1β+IL-6+IL-23组中最高，而在TGF-β组中最低。预后不良患者CSF中的Th17明显高于预后良好患者。
结论
NMDAR脑炎患者Th17细胞比例及相应促分化细胞因子表达增加，且Th17与患者的治疗及预后密切相关。Th17细胞在抗NMDAR脑炎的发病及进展中起关键作用。
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