关于多发性硬化中浆样树突状细胞的研究进展

多发性硬化是中枢神经系统炎症性自身免疫性疾病的典型代表,以白质脱髓鞘为主要特征。浆样树突状细胞,是专职抗原提呈细胞,是固有免疫和适应性免疫的桥梁,在启动初级免疫应答和维持免疫耐受中发挥了重要作用。由于浆样树突状细胞可以产生大量的细胞因子,特别是Ⅰ型干扰素,所以它与抗炎、免疫调节联系紧密。而目前Ⅰ型干扰素(β)被认为是治疗多发性硬化的有效的免疫调节剂。本文就浆样树突状细胞的来源、特性及其在固有免疫、适应性免疫及免疫耐受中的作用机制进行系统归纳整理,并就其未来发展前景做一简单介绍,为进一步探索免疫调节新机制和寻求多发性硬化新的治疗靶点提供理论依据和基础。     

多发性硬化中适应性免疫细胞的致病机制

多发性硬化(multiple sclerosis, MS)是发生于中枢神经系统(central nervous system, CNS)的慢性进行性免疫炎性疾病,伴随少突胶质细胞、神经元和轴索的破坏。近年来研究发现,外周淋巴细胞(包括T细胞、B细胞及其亚群)在中枢神经系统的浸润作为MS的早期标志之一,在其发病和发展中起到重要作用,但其中许多细胞亚群的具体作用机制尚不明确。该综述通过总结最新研究结果,探讨外周适应性免疫细胞与中枢神经系统炎症关系以及不同种类适应性免疫细胞在MS中行使的功能。     

Act1介导的IL-17信号通路与自身免疫性脑脊髓炎关系的研究进展

多发性硬化(multiple sclerosis,MS)是以中枢神经系统(central nervous system,CNS)慢性炎症性脱髓鞘为主要特征的自身免疫性疾病。实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)在发病特点和病理学特征上与人类的MS表现非常相似,是研究MS发病机制及治疗的理想的动物模型。辅助性T细胞17(T helper cell 17,Th17)细胞是CD4~+T细胞的一个重要亚群,主要分泌IL-17(interleukin-17)细胞因子,在EAE的发病过程中具有重要作用。NF-κB激活剂1(NF-κB activator 1,Act1)是SEFIR(similar expression to fibroblast growth factor genes/IL-17R)蛋白家族的一员,是IL-17信号通路的连接蛋白。在IL-17的刺激下,Act1通过SEFIR-SEFIR相互作用招募到IL-17受体(IL-17 receptor,IL-17R)上,以调节下游信号通路。对Act1介导的IL-17信号与自身免疫性疾病的关系做一综述,以期为EAE的发病机制研究和治疗提供重要的理论基础和分子靶标。     

自身免疫性疾病治疗性疫苗研究进展

自身免疫性疾病的发生与体内自身反应性T／B细胞的异常活化有关。病理性自身免疫应答是多发性硬化、重症肌无力等自身免疫性疾病的主要致病原因。针对已感染致病原的无症状携带者或发病的患者的自身免疫性疾病治疗性疫苗能特异性地调节异常的免疫应答,具有重要的理论价值和应用前景。     

多发性硬化实验动物模型的研究与应用进展

多发性硬化(multiple sclerosis,MS)是一种中枢神经系统慢性炎症性脱髓鞘疾病,为临床神经系统的疑难重病,基本病理特征包括炎症浸润,原发性脱髓鞘和胶质细胞活化等。其病理过程、发病机制的研究以及治疗药物的筛选和评价都需要合适的动物模型。本文从其发病机制、致病特点与适应范围等方面对MS模型研究进展进行介绍。     

细胞自噬在多发性硬化中的作用

多发性硬化(multiple sclerosis,MS)是一种以白质脱髓鞘、胶质细胞增殖、轴突损伤和进行性神经功能障碍为主要特点的中枢神经系统慢性炎症脱髓鞘疾病,其病因和发病机制尚未完全明确。既往在对MS及其动物模型实验性自身免疫性脑脊髓炎的研究中发现了细胞自噬也参与了其发病,涉及到的主要有T淋巴细胞、B淋巴细胞、小胶质细胞、少突胶质细胞、星形胶质细胞、树突状细胞、神经元。因此,本文将对以上细胞自噬在MS中的作用进行综述,以期为研究MS的发病机制和治疗研究提供参考。     

网膜素在神经关联疾病中的生物标记物作用

网膜素(omentin)是一种新型的脂肪因子,由内脏脂肪组织分泌。研究发现,网膜素在脑梗死、成神经细胞瘤、多发性硬化等神经关联疾病中发挥着重要作用,并与疾病的发生、发展具有良好相关性。因此,网膜素或可成为神经关联疾病的生物标记物,为相关疾病的诊断、治疗和预后评估提供新指标。     

多发性硬化和视神经脊髓炎的体液免疫机制及其干预策略

多发性硬化(multiple sclerosis,MS)和视神经脊髓炎(neuromyeltis optica,NMO)是两个独立的中枢神经系统炎性脱髓鞘疾病,B细胞和体液免疫在二者发生发展中发挥了重要作用。越来越多证据显示,针对B细胞和/或抗体的治疗有可能同时对抗MS和NMO。就B细胞及其体液免疫在MS和NMO发生发展及治疗中的作用做一综述。     

CD8+T细胞在多发性硬化中的致病性作用

多发性硬化是T细胞介导的自身免疫性疾病。先前对它的研究大多集中在CD4 T细胞的致病和调节性作用上,但是,近几年来越来越多的证据表明CD8 T细胞也参与多发性硬化的病理损伤过程。 CD8 T细胞存在于MS病灶部位,髓鞘抗原特异性CD8 T细胞也从MS患者的血液和脑脊液中分离得到,CD8 T细胞通过直接杀伤或释放细胞因子和趋化因子等间接参与MS的病理过程。本文就近几年关于CD8 T细胞在多发性硬化中的致病性作用的研究进展予以介绍。     

Th17分化调控与多发性硬化症及其治疗新策略

多发性硬化症(multiple sclerosis, MS)是一种由T细胞介导、以中枢神经脱髓鞘及神经元病变为主要病理特征的自身免疫性疾病。该病的致病机制尚未明确,且目前无法彻底治愈,只能通过药物来缓解病理进程。因此,寻找MS的有效治疗途径尤为重要。研究发现,Th17细胞与MS疾病的发生与发展密切相关,而T细胞分化为Th17细胞又受到多方面因素的影响,其中miRNA和代谢程序调控在此过程中发挥重要作用。现对Th17细胞及MS相关的最新研究进展进行综述,重点讨论了Th17细胞的分化调控和MS治疗的一些新策略。     

Towards immunotherapeutic drugs and vaccines against multiple sclerosis

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Numerous treatment options are available to MS patients; however, these options need to be improved. Herein, we review the current drugs and therapeutic approaches available to MS patients, preclinical trial interventions and recent animal model studies for the potential therapy of MS. Since the current treatment of MS remains elusive and is limited, animal studies and clinical research offers an optimistic outlook.     

Systemic infections in multiple sclerosis and experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). It has been suggested that viral and bacterial infections contribute to the pathogenesis of MS. This review will give an overview about the influence of viral and bacterial infections on MS and experimental autoimmune encephalomyelitis (EAE). It will focus on bacterial infections and will also emphasise therapeutic consequences such as the impact of antibiotic treatment on the course of EAE. In summary, a growing body of evidence suggests that systemic infections are a risk factor for the initiation of autoimmune processes including the induction of acute events in MS. Experimental and clinical data strongly suggest early treatment of bacterial infections in MS patients to avoid aggravation and relapse.     

Biomarker Studies in Multiple Sclerosis: From Proteins to Noncoding RNAs

Multiple sclerosis (MS) is a neuroimmunological disorder characterized by central nervous system demyelination, axonal injury and loss. Considering the complexity of its aetiopathogenesis, early diagnosis of MS and individualized management are challenging in clinical practice. As the pathophysiologic and pharmacological indicators, studies on biomarkers in MS are useful for early prediction and diagnosis, monitoring of disease activity and predicting treatment response. In this review, we will summarize recent development of biomarker studies in MS from protein molecules to noncoding RNAs.     

A review of possible therapies for multiple sclerosis

Molecular and Cellular Biochemistry - Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system with a wide range of symptoms, like executive function...     

Glutamate excitotoxicity in a model of multiple sclerosis

Glutamate excitotoxicity mediated by the AMPA/kainate type of glutamate receptors damages not only neurons but also the myelin-producing cell of the central nervous system, the oligodendrocyte. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system. Because glutamate is released in large quantities by activated immune cells, we expected that during inflammation in MS, glutamate excitotoxicity might contribute to the lesion. We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced dephosphorylation of neurofilament H, an indicator of axonal damage. Despite the clinical differences, treatment with NBQX had no effect on lesion size and did not reduce the degree of central nervous system inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect on the immune system. Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for multiple sclerosis.     

The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis

Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) for which there is no efficacious cure. Thanks to numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been made available recently. Still, there is a terrible need for compounds capable of reducing the severity of the autoimmune attack and of blocking progression of the disorder. Also, besides the classic immunosuppressive strategies, it is now appreciated that compounds directly targeting neuronal death can be of relevance to the treatment of MS patients. Acetylation homeostasis is a key regulator of both immune cell activation and neuronal survival. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. In this review, we provide an appraisal of the literature on HDACi and MS, also discussing the mechanisms by which HDACi can suppress the autoimmune attack to the CNS.     

Contribution of peptides to multiple sclerosis research

Multiple sclerosis (MS) is an autoimmune disease associated with chronic inflammatory demyelination of the central nervous system in genetically susceptible individuals. Because of the disease complexity and heterogeneity, its pathogenesis remains unknown despite extensive research efforts, and specific effective treatments have not yet been developed. Peptide-based research has been important in attempts to unravel particular aspects of this complex disease, including the characterization of the different molecular mechanisms of MS, with the goal of providing useful products for immune-mediated therapies. In fact, in the past decade, peptide-based research has been predominant in research aimed to identify and/or develop target antigens as synthetic probes for specific biomarkers as well as innovative immunomodulating therapies. This review presents an overview of the contributions of peptide science to MS research and discusses future directions of peptide-based investigations.     

Oral Colonization by Candida Species in Patients with Multiple Sclerosis

Mycopathologia - Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease,...     

多发性硬化疾病及模型小鼠中疾病相关细胞因子和转录因子研究进展

多发性硬化症（multiple sclerosis,MS）是一种原发于中枢神经系统的炎症性脱髓鞘疾病。实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis,EAE）与MS有相似的临床症状和病理特征,是被广泛应用于人类疾病研究的动物模型。MS确切的发病机制尚不清楚,但普遍认为是在易感基因的基础上,受环境因素触发,由CD4＋T细胞介导的中枢神经系统（centralnervous system,CNS）自身免疫性疾病。初始CD4＋T细胞在T细胞受体介导下活化,继而可分化为至少4个主要亚型,分别为TH1、TH2、TH17和iTreg细胞,参与不同类型的免疫应答。细胞因子和转录因子网络对CD4＋T细胞分化和效应细胞因子产物有重要意义。该文综述了各相关细胞因子和转录因子在CD4＋T细胞向不同亚型分化及MS/EAE发病过程中的相互作用和调控,揭示各因子在这些过程中的作用,有助于进一步研究和治疗MS。     

Quantitative Proteome Analysis of Brain Subregions and Spinal Cord from Experimental Autoimmune Encephalomyelitis Mice by TMT‐Based Mass Spectrometry

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, the aim is to build a proteome map of the biological changes that occur during MS at the major onset sites—the brain and the spinal cord. Quantitative proteome profiling is performed in five specific brain regions and the spinal cord of EAE and healthy mice with high‐resolution mass spectrometry based on tandem mass tags. On average, 7400 proteins per region are quantified, with the most differentially expressed proteins in the spinal cord (1691), hippocampus (104), frontal cortex (83), cerebellum (63), brainstem (50), and caudate nucleus (41). Moreover, region‐specific and commonly expressed proteins in each region are identified and bioinformatics analysis is performed. Pathway analysis reveals that protein clusters resemble their functions in disease pathogenesis (i.e., by inducing inflammatory responses, immune activation, and cell–cell adhesion). In conclusion, the study provides an understanding of the pathogenesis of MS in the EAE animal model. It is expected that the comprehensive proteome map of the brain and spinal cord can be used to identify biomarkers for the pathogenesis of MS.