关于 NKG2D 配体在多发性硬化症和其他自身免疫性疾病中的作用的现有知识。

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Frontiers in Molecular Neuroscience Pub Date : 2025-01-10 eCollection Date: 2024-01-01 DOI:10.3389/fnmol.2024.1493308
Aleksandra Pogoda-Wesołowska, Nina Sługocka, Agnieszka Synowiec, Klaudia Brodaczewska, Marcin Mejer-Zahorowski, Maciej Ziękiewicz, Wojciech Szypowski, Piotr Szymański, Adam Stępień
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引用次数: 0

摘要

多发性硬化症(MS)是一种慢性中枢神经系统(CNS)疾病,具有脱髓鞘炎症特征。它是影响年轻人的最常见的非创伤性致残性疾病。多发性硬化症的发病率和患病率呈上升趋势。然而,其确切原因尚不清楚。用于支持诊断的主要测试是磁共振成像(MRI)检查和脑脊液(CSF)分析。尽管如此,到目前为止,还没有发现敏感的或特定的标记物,可以在疾病的初始阶段检测到这种疾病。近年来,研究人员关注的事实是,MS患者外周血、CSF和脑组织中c型凝集素样受体+ (NKG2D+) T细胞的自然杀伤细胞组2成员D (NKG2D)家族的数量高于对照组。属于NKG2D的激活受体受到特定配体的刺激:在人类中,这些配体是主要的组织相容性复合体(MHC) I类多肽相关序列A (MICA)和MHC I类多肽相关序列B (MICB)蛋白和UL16结合1-6蛋白(ULBP1-6)。在生理条件下,上述配体的表达水平较低或检测不到,但可以在应激因素的诱导下表达。NKG2D配体(nkg2dl)参与其表达的表观遗传调控。迄今为止,对细胞培养、动物模型和脑组织的研究表明,MS患者的少突胶质细胞和星形胶质细胞中MICA/B、ULPB4及其小鼠同源小鼠UL16结合蛋白样转录物(MULT1)的表达升高。此外,与对照组相比,MS患者血浆和脑脊液中的可溶性nkg2dl含量升高。在这篇综述中,我们的目的是描述NKG2D和nkg2dl的作用,以及它们在MS发病机制中的相互作用,以及在其他自身免疫性疾病如类风湿关节炎(RA)、炎症性肠病(IBD)、系统性红斑狼疮(SLE)和乳糜泻(CeD)中的作用。我们还评估了这些蛋白作为诊断标记物的潜力,并考虑了NKG2D配体及其通路作为MS治疗靶点的未来前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The current state of knowledge on the role of NKG2D ligands in multiple sclerosis and other autoimmune diseases.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with demyelinating inflammatory characteristics. It is the most common nontraumatic and disabling disease affecting young adults. The incidence and prevalence of MS have been increasing. However, its exact cause remains unclear. The main tests used to support the diagnosis are magnetic resonance imaging (MRI) examination and cerebrospinal fluid (CSF) analysis. Nonetheless, to date, no sensitive or specific marker has been identified for the detection of the disease at its initial stage. In recent years, researchers have focused on the fact that the number of natural killer cell group 2 member D (NKG2D) family of C-type lectin-like receptor + (NKG2D+) T cells in the peripheral blood, CSF, and brain tissue has been shown to be higher in patients with MS than in controls. The activating receptor belonging to the NKG2D is stimulated by specific ligands: in humans these are major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) proteins and UL16 binding 1-6 proteins (ULBP1-6). Under physiological conditions, the aforementioned ligands are expressed at low or undetectable levels but can be induced in response to stress factors. NKG2D ligands (NKG2DLs) are involved in epigenetic regulation of their expression. To date, studies in cell cultures, animal models, and brain tissues have revealed elevated expression of MICA/B, ULPB4, and its mouse homolog murine UL16 binding protein-like transcript (MULT1), in oligodendrocytes and astrocytes from patients with MS. Furthermore, soluble forms of NKG2DLs were elevated in the plasma and CSF of patients with MS compared to controls. In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.

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来源期刊
CiteScore
5.70
自引率
2.10%
发文量
669
审稿时长
14 weeks
期刊介绍: Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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