Itou Tatsuo, Fujita Koji, Okuzono Yuumi, Warude Dnyaneshwar, Miyakawa Shuuichi, Mihara Yoshimi, Matsui Naoko, Morino Hiroyuki, Kikukawa Yusuke, Izumi Yuishin
Oncology Drug Discovery Unit Japan, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.
Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
J Neuroinflammation. 2024 Dec 27;21(1):331. doi: 10.1186/s12974-024-03327-w.
The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS. Our analysis revealed increased frequencies of T helper 17 cells (Th17) relative to regulatory T cells, effector CD8 T cells relative to naïve CD8 T cells, and CD16CD56 mature natural killer cells relative to CD16CD56 naïve natural killer cells in patients with rapidly progressive ALS. Additionally, we employed serum proteomics through a proximity extension assay combined with next-generation sequencing to identify inflammation-related proteins associated with rapid disease progression. Among these proteins, interleukin-17 A correlated with the frequency of Th17, while killer cell lectin-like receptor D1 (CD94) correlated with the frequency of effector CD8 T cells. These findings further support the active roles played by these specific immune cell types in the progression of ALS.
免疫系统因其与肌萎缩侧索硬化症（ALS）疾病进展的关联而备受关注。然而，外周免疫细胞在此背景下的作用仍存在争议。在此，我们对外周血单个核细胞进行了单细胞RNA测序，以全面分析与ALS患者疾病进展速度相关的免疫细胞。我们的分析显示，在疾病快速进展的ALS患者中，辅助性T细胞17（Th17）相对于调节性T细胞的频率增加，效应性CD8 T细胞相对于初始CD8 T细胞的频率增加，以及CD16CD56成熟自然杀伤细胞相对于CD16CD56初始自然杀伤细胞的频率增加。此外，我们通过邻近延伸分析结合下一代测序采用血清蛋白质组学来鉴定与疾病快速进展相关的炎症相关蛋白。在这些蛋白中，白细胞介素-17 A与Th17的频率相关，而杀伤细胞凝集素样受体D1（CD94）与效应性CD8 T细胞的频率相关。这些发现进一步支持了这些特定免疫细胞类型在ALS进展中所起的积极作用。
