Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis
Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis
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DOI：
10.1038/s41598-020-62756-8
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发表时间：
2020-04-03
影响因子：
4.6
通讯作者：
Ziemssen, Tjalf
中科院分区：
文献类型：
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作者：
Jin, Mengmeng;Guenther, Rene;Ziemssen, Tjalf
神经炎症参与肌萎缩侧索硬化症（ALS）的发病机制，但只有有限的数据可用于系统的外周和中枢免疫细胞在ALS。我们研究了73例ALS患者和48名健康对照（对照）的外周血中的免疫荧光激活细胞分选以及血清中的细胞因子表达谱的详细资料。在16名ALS患者和10名对照的亚组中，我们另外研究了脑脊液（CSF）样本。在外周血中，T细胞亚型向促炎性Th 1和Th 17细胞转变，而抗炎性Th 2和T调节细胞减少。与对照组相比，ALS患者先天免疫中的重要参与者，包括不同的单核细胞（Mo）和自然杀伤（NK）细胞亚型发生了变化。促炎血清细胞因子如白细胞介素（IL）-1 β、IL-6和干扰素-γ（IFN-γ）升高，抗炎细胞因子IL-10降低。相关分析显示Th 1和Th 17与ALS功能评定量表修订版（ALSFRS-R）和用力肺活量呈中度负相关。在CSF样本中，没有相关的改变的免疫profileswerenfound. In结论，在ALS的免疫模式转向Th 1/Th 17细胞介导的促炎性免疫反应，并与疾病的严重程度和进展。需要大规模的前瞻性研究来证实这些发现。
Neuroinflammation is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), but only limited data are available on systematic peripheral and central immune cell profiles in ALS. We studied detailed immune profiles of 73 ALS patients and 48 healthy controls (controls) in peripheral blood by fluorescence-activated cell sorting as well as cytokine expression profiles in serum. In a subgroup of 16 ALS patients and 10 controls we additionally studied cerebrospinal fluid (CSF) samples. In peripheral blood, T cell subtypes presented a shift towards pro-inflammatory Th 1 and Th 17 cells whereas anti-inflammatory Th2 and T regulatory cells were decreased. Important players in innate immunity including distinct monocyte (Mo) and natural killer (NK) cell subtypes were changed in ALS patients compared to controls. Pro-inflammatory serum cytokines such as interleukin (IL)-1 beta, IL-6 and interferon-gamma (IFN-gamma) were increased and the anti-inflammatory cytokine IL-10 was decreased. Correlation analysis revealed moderate negative correlations between Th1 and Th17 to the ALS functional rating scale revised (ALSFRS-R) and to forced vital capacity. In CSF samples, no relevant alteration of the immune profile was found. In conclusion, the immune profile in ALS was shifted towards a Th1/Th17 cell-mediated pro-inflammatory immune response and correlated to disease severity and progression. Large prospective studies are needed to confirm these findings.