Gaur Nayana, Huss Elena, Prell Tino, Steinbach Robert, Guerra Joel, Srivastava Akash, Witte Otto W, Grosskreutz Julian
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Jena Centre for Healthy Ageing, Jena University Hospital, Jena, Germany.
Front Neurol. 2021 May 14;12:629332. doi: 10.3389/fneur.2021.629332. eCollection 2021.
Neuroinflammation significantly contributes to Amyotrophic Lateral Sclerosis (ALS) pathology. In lieu of this, reports of elevated chitinase levels in ALS are interesting, as they are established surrogate markers of a chronic inflammatory response. While post-mortem studies have indicated glial expression, the cellular sources for these moieties remain to be fully understood. Therefore, the objective of this pilot study was to examine whether the peripheral immune system also contributes to chitinase dysregulation in ALS. The temporal expression of CHIT1, CHI3L1, and CHI3L2 in non-polarized monocyte-derived macrophages (MoMas) from ALS patients and healthy controls (HCs) was examined. We demonstrate that while CHIT1 and CHI3L1 display similar temporal expression dynamics in both groups, profound between-group differences were noted for these targets at later time-points i.e., when cells were fully differentiated. CHIT1 and CHI3L1 expression were significantly higher in MoMas from ALS patients at both the transcriptomic and protein level, with CHI3L1 levels also being influenced by age. Conversely, CHI3L2 expression was not influenced by disease state, culture duration, or age. Here, we demonstrate for the first time, that in ALS, circulating immune cells have an intrinsically augmented potential for chitinase production that may propagate chronic neuroinflammation, and how the ageing immune system itself contributes to neurodegeneration.
神经炎症在肌萎缩侧索硬化症（ALS）的病理过程中起着重要作用。鉴于此，ALS患者中几丁质酶水平升高的报道很有意思，因为它们是慢性炎症反应的既定替代标志物。虽然尸检研究表明胶质细胞有表达，但这些分子的细胞来源仍有待充分了解。因此，本初步研究的目的是检验外周免疫系统是否也在ALS中导致几丁质酶失调。研究了来自ALS患者和健康对照（HC）的非极化单核细胞衍生巨噬细胞（MoMas）中CHIT1、CHI3L1和CHI3L2的时间表达情况。我们证明，虽然CHIT1和CHI3L1在两组中表现出相似的时间表达动态，但在较晚的时间点，即细胞完全分化时，这些靶点在组间存在显著差异。在转录组和蛋白质水平上，ALS患者的MoMas中CHIT1和CHI3L1的表达均显著更高，CHI3L1水平也受年龄影响。相反，CHI3L2的表达不受疾病状态、培养时间或年龄的影响。在此，我们首次证明，在ALS中，循环免疫细胞具有内在增强的几丁质酶产生潜力，这可能会加剧慢性神经炎症，以及衰老的免疫系统本身如何导致神经退行性变。
