用于治疗免疫性疾病的完全人源化抗IL-17单克隆抗体Secukinumab

白细胞介素IL-17是一种重要的炎症细胞因子,与炎症、肿瘤、过敏性疾病、自身免疫性疾病等的发生发展有着密切关系,在体内主要由CD4＋T细胞（如Th17细胞）产生,也可由巨噬细胞、星形细胞、     

17型辅助T细胞的生物学特性及免疫学效应研究进展

目的:探讨17型辅助T细胞(简称Th17细胞)的生物学特性及其在机体免疫调节中的作用,为相关药物治疗提供理论依据。方法:综述文献,分析了Th17细胞的分泌因子,总结了正负调节Th17细胞分化的影响因素以及Th17细胞与自身免疫性疾病、1型辅助T细胞(Th1细胞)、调节性T细胞(Treg细胞)的关系。结果:Th17细胞分泌因子包括白介素-17(IL-17)、IL-17F、IL-21、IL-22等;Th17细胞增多与移植排斥、自身免疫性疾病密切相关;IL-6、转化生长因子-β、IL-23和IL-1促进Th17细胞分化,IL-2、IL-25、IL-27、细胞因子信号抑制因子3和维甲酸等抑制Th17细胞分化;Th17细胞通过IL-17参与自身免疫性疾病的发生,与Th1细胞在发挥效应的过程中存在协同关系,与Treg细胞对免疫系统的调节作用相反。结论:Th17细胞亚群的鉴定、分化调节机制及其免疫学效应的研究将为治疗复杂的自身免疫性疾病、难以控制的炎症及病原体感染提供重要的药物和生物靶点依据。     

Th17/Treg平衡在类风湿关节炎中作用的研究进展

类风湿性关节炎(rheumatoid arthritis,RA)是一种以慢性多关节滑膜炎为主要特征的自身免疫性疾病。虽然目前对于RA的确切发病机制尚不明确,但一般认为和T细胞相关。最近研究发现调节性T细胞(regulatory T cell,Treg)和Th17细胞在RA的发生发展中发挥重要作用。Th17细胞能够分泌促炎症因子IL-17,通过诱导基质金属蛋白酶(ma-trix metallo proteinases,MMPs)和破骨细胞生成,促进骨滑膜炎症、骨和关节损伤;而Treg则通过释放抑制性细胞因子IL-10和TGF-β发挥免疫效应,调控RA中的炎症性免疫应答过程。单独TGF-β作用下诱导初始T细胞分化为Treg,而在TGF-β和IL-6共同作用下诱导初始T细胞分化为Th17细胞,因此,Th17和Treg细胞在特定的细胞因子微环境下可以相互转化。调节Th17/Treg之间的平衡可能成为治疗RA的新方法。该文将对Th17/Treg平衡在RA发生发展中的调节作用作一综述。     

Treg细胞与Th17细胞的研究现状及临床意义

CD4+辅助性T细胞是一类重要的免疫调节细胞.传统观点认为CD4+辅助性T细胞,特别是Th1和Th2细胞能够反映机体的免疫功能状态.CD4+CD25+调节性T细胞(regulatory tcells, Treg)和辅助T细胞17是新发现的Th细胞亚群,它们在维持机体免疫平衡方面发挥重要作用[1-3],是对Th1和Th2免疫平衡理论的重要补充,成为免疫学和肿瘤学等领域的研究热点[4].炎症、感染、肿瘤、自身免疫性疾病等多种疾病状态中Th17、Treg细胞免疫失衡也有不少报道[5-7].本文就Treg细胞及Th17细胞的研究现状及临床意义做一综述.     

Tet调控Th17/Treg细胞分化参与自身免疫性疾病发病的研究进展

CD4⁺ T细胞是人体免疫重要的一部分,其中辅助性T细胞17（T helper cell 17,Th17）和调节性T细胞（regulatory T cells,Treg）两个新近发现的CD4⁺ T细胞亚群在自身免疫疾病的发生发展中也起关键作用。Th17细胞能够引起自身免疫和炎性反应,而Treg细胞抑制疾病发生并维持免疫稳态;10～11易位蛋白（ten-eleven translocation,Tet）作为DNA去甲基化的关键因子,当其缺失时能够影响Th17/Treg免疫平衡。本文针对Tet调控Th17/Treg细胞分化参与自身免疫疾病发生发展的研究进展作一综述。     

Th17细胞与银屑病关系的研究进展

Th17细胞是近年来发现的一种CD4^＋T细胞新亚型,并与银屑病及其他自身免疫性疾病的发病密切相关。Th17细胞主要通过IL-23／Th17细胞轴引起并加剧银屑病患者皮损中慢性免疫性炎症,由Th17细胞产生的IL-22在银屑病的发病机制中发挥关键作用。Th17细胞是如何由外周组织迁移到真皮层？Th17细胞与银屑病的发生和加重有何关系？了解Th17细胞分化所需要的特殊转录因子、表面表达分子、分泌的细胞因子对进一步认识银屑病免疫病理过程及发现潜在治疗靶点有很大帮助。     

复方甘草酸苷对寻常型银屑病患者外周血辅助性T细胞17相关细胞因子影响的研究

<正>银屑病是一种由T细胞介导的免疫性皮肤病,主要与辅助性T细胞(Th)1、Th17相关,而近年来研究发现白细胞介素(IL)-23/Th17轴在银屑病的发病中起重要作用,Th17细胞分泌IL-17、IL-22等细胞因子,是重要的炎症介质[1,2]。IL-23作为一个前炎症因子,促进Th17细胞的分化、活化,并且对     

Th17细胞在自身免疫性疾病中的研究进展

经典的Th1和Th2模式为人们理解CD4+T细胞的生物学特性以及固有免疫和适应性免疫提供了基本框架.近来,新发现的Th17细胞以优先产生IL-17、IL-17F和IL-22等细胞因子为特征,它不仅参与宿主防御免疫而且在自身免疫方面起重要作用.这种新的效应T细胞的发现改变了传统的对宿主免疫防御、免疫调节和免疫致病的理解.此文就Th17细胞在自身免疫性疾病中的研究进展作一综述.     

辅助性T细胞17及白介素-17在儿童过敏性紫癜的表达及意义

目的：探讨过敏性紫癜患儿急性期外周血辅助性T细胞17（Th17）和白介素17（IL-17）水平的变化及意义。方法将研究对象分为过敏性紫癜皮肤型（HSP）组30例,过敏性紫癜性肾炎（HSPN）组30例,健康对照组30例。抽取外周血采用ELISA法检测IL-17水平,流式细胞术检测Th17细胞数。 HSP组和HSPN组在急性发作时、治疗前抽血检测IL-17水平和Th17细胞数。结果 HSP组和HSPN组患儿外周血Th17细胞数及IL-17水平较健康对照组明显增高（P均〈0.05）,但HSPN组患儿Th17细胞数和IL-17水平与HSP组患儿比较差异无统计学意义（P〉0.05）。结论过敏性紫癜患儿急性期血浆IL-17水平增高,Th17细胞功能增强;Th17细胞和IL-17共同参与儿童过敏性紫癜的发病机制。血浆IL-17水平是HSP活动的指标之一,并且可能成为HSP早期的重要生物学标记。     

系统性红斑狼疮Th17细胞分子调控机制研究进展

系统性红斑狼疮(SLE)是一种典型的多系统炎症性自身免疫性疾病,发病机制复杂。Th17细胞是一种以分泌IL-17为主的CD4⁺T细胞亚群,与肿瘤、感染、过敏以及自身免疫性疾病等相关。Th17细胞生物学特性及其相关的细胞因子与其致病机制密切相关,研究发现Th17细胞在SLE的发生发展中发挥重要作用。归纳近年来Th17细胞的研究进展,探讨其在SLE可能的发病机制,为治疗提供新的依据。     

The importance of reendothelialization after arterial injury

Atherosclerosis is still the principal cause of morbidity and mortality in Western countries and although a significant progress has been made in the understanding of its pathophysiology, the determinants of atherosclerotic plaque instability are still poorly understood. The endothelium plays a pivotal role for the development, progression, and complication of atherosclerosis. Endothelial dysfunction is widely recognized as one of the early alteration in the vessel wall preceding the development of the plaque. However, considering the plethora of vascular functions which are regulated by endothelium, it plays a pivotal role throughout the atherosclerotic process and indeed the loss of endothelial cells, leading to plaque denudation, is one of the main causes of plaque complication. It is therefore conceivable that the maintenance of the endothelial layer physical continuity and function is crucial for the prevention of atherosclerosis. In the presence of cardiovascular risk factors, endothelial cells are continuously injured and repaired by the proliferation of resident cells and circulating endothelial progenitor cells. Indeed the number of circulating endothelial progenitor cells has been identified as an predictor of cardiovascular events. The increase in bone marrow release of endogenous progenitor cells or the enhancement of their homing in arterial denuded sites or in intravascular stent surface, are currently pursued to reduce atherosclerosis development/complication and intrastent restenosis, respectively. However, some challenges may arise from procedures enhancing endothelialization, including unwanted angiogenesis which may favor neoplasia progression and paradoxically atherosclerotic plaque expansion and complication.     

Secukinumab (AIN-457) for the treatment of Psoriasis

Secukinumab (also known as AIN-457) is a human monoclonal antibody targeting IL-17A, which has been recently FDA-approved for the treatment of moderate to severe psoriasis and psoriatic arthritis with coexistent moderate to severe plaque psoriasis based on clinical trials demonstrating excellent efficacy. This review will address the rationale for targeting the IL-23/Th17/IL-17 axis, the role of IL-17 and Th17 cells in psoriasis and other chronic inflammatory diseases, and will examine pre-clinical studies, pharmacologic properties, clinical efficacy, and the safety profile of secukinumab.     

失巢凋亡在As斑块破裂中的作用及机制

失巢凋亡是一种特殊形式的细胞程序性死亡,不仅参与了机体组织自身平衡的调节,而且还参与了许多病理过程的发生,如动脉粥样硬化(atherosclerosis,As)、急性冠脉综合征、心力衰竭、动脉瘤和肿瘤等。该文综述了失巢凋亡在As斑块不稳定性和破裂中的作用及机制。     

Atherosclerosis as an inflammatory disease

In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell typespecific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vascular endothelial cells, smooth muscle cells and human macrophages in vitro as well as in situ in human atherosclerotic lesions. Recent studies indicate that CD40L activates atheroma-associated cells by promoting the expression of molecules thought to be involved in atherosclerosis, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor. Atherosclerosis starts with an innate immune response involving the recruitment and activation of monocytes macrophages that respond to an excessive accumulation of modified lipids within the arterial wall, followed by an adaptive immune response involving antigen-specific T lymphocytes. Effector T cells recognize modified auto-antigens such as oxidized LDL and heat shock proteins (i.e. HSP-60) that are presented by antigen-presenting cells such as macrophages or dendritic cells. The accumulation of inflammatory cells within the arterial wall leads to local production of chemokines, interleukins and proteases that enhance the influx of monocytes and lymphocytes, thereby promoting the progression of atherosclerotic lesions Recent reports have helped explain some of these questions by pointing to a role of contact dependent interaction between CD40 and CD40 ligand (CD40L, renamed CD154) as a stimulus for atheroma-associated cells. Also Macrophages play important roles in the progression of atherosclerosis by exhibiting unique characteristics under the various stimuli, evolving the plaque instability, thrombus formation and remodeling. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.     

Th17细胞在类风湿关节炎发病机制中的作用研究进展

类风湿关节炎(rheumatoid arthritis,RA)是临床常见炎症性自身免疫疾病,以早期进行性关节滑膜炎症为主要临床特征,晚期则多以关节软骨破坏及骨侵蚀为主要病理特征。RA病因复杂,病理机制至今未明,发病率高,5年期致残率高。Th17细胞作为CD4+T细胞的亚群之一,其分泌的IL-17、IL-21等促炎性细胞因子,在RA关节滑膜炎症和关节软骨破坏及骨侵蚀等多个病理环节均发挥重要作用。基于此,本文对近年来Th17细胞参与RA关节滑膜炎症和关节软骨破坏及骨侵蚀病程的相关研究文献进行综述和讨论,以期为RA发病机制研究提供新思路,为以Th17细胞为作用靶点的创新药物开发提供参考。