B7-CD28/CTLA4共刺激途径在再生障碍性贫血免疫机制中作用

T淋巴细胞是细胞免疫反应中的主要效应细胞,细胞免疫应答的中心环节是T细胞对抗原的识别和有效激活,即T细胞激活的的双信号机制,其中TCR与MHC-Ag复合物的结合为第一信号;递呈细胞(APC)提供的协同刺激信号为第二信号。T细胞上的CD28/ CTLA4与抗原递呈细胞上的B7分子[B7-1(CD80),B7-2(CD86)]是目前发现的最为重要的协同刺激分子,它们在自身免疫病患者T细胞及抗原递呈细胞上有异常表达,且参与致病过程。这些分子及其同系物与受体结合后,在T细胞免疫应答的不同阶段中起着重要的调节作用,涉及整个免疫系统中细胞免疫和体液免疫正向负向调节的诸多方面。正确理解这些通路将为自身免疫性疾病的治疗提供新的前景。     

CD200及其信号通路与自身免疫病的相关性研究

 CD200是一种I型跨膜糖蛋白，在人体内分布十分广泛，但其受体主要分布于髓系细胞。大量研究发现，CD200介导的通路在调节免疫应答中起重要作用，对该通路的调节可影响自身免疫病的发生发展。此文就CD200的结构、表达、功能及其对自身免疫病的影响进行综述。     

抗CD22单克隆抗体治疗自身免疫病研究进展

CD22是特异性表达于B淋巴细胞上的Ⅰ型跨膜糖蛋白，属于免疫球蛋白超家族中唾液酸黏附素家族成员，其作为抑制性辅助受体在B细胞的调节与体液免疫中发挥重要作用。自身免疫病是由自身免疫失调所致，B细胞异常激活以及致病性自身抗体的生成是自身免疫病的重要特征之一。通过抗CD22单克隆抗体治疗B细胞异常增殖活化介导为主的自身免疫病，如系统性红斑狼疮和类风湿性关节炎等，已引起关注。此文就CD22的分子特征、功能以及靶向CD22治疗自身免疫相关性疾病的研究进展进行综述。     

JAK/STAT信号通路与白血病

JAK／STAT通路是造血生长因子广泛应用的信号转导通路．介导细胞多种生理过程，JAK／STAT通路在生物个体发生发育、造血调节和免疫反应中发挥着重要的作用。JAK／STAT信号通路的持续激活与人类多种肿瘤尤其是造血系统恶性肿瘤的发生有关。JAK／STAT通路的持续激活已成为白血病的普遍特征。本对近年来自血病形成中JAK／STAT的异常激活的研究综述如下。     

程序性死亡分子1及其配体与自身免疫病的研究进展

程序性死亡分子1 (programmed death-1,PD-1)及其配体(programmed death-1 ligand,PD-L)是一对新近研究较多的负性共刺激分子.PD-1与其配体结合后,传导的信号能抑制T淋巴细胞增殖,在调节T细胞活化和免疫耐受过程中发挥关键作用,从而对防止自身免疫病的发生、发展具有重要作用.PD-1/PD-L在免疫调节中的作用使其有望成为治疗免疫性疾病新的靶向分子.     

P13K/Akt信号转导通路的研究进展

PI3K/Akt信号传导通路在恶性肿瘤的发生、发展、治疗及转归中发挥着重要作用,PI3K作为联系胞外信号与细胞应答效应的桥梁分子,在一系列上游或旁路信号分子的影响下,作用于下游的信号分子对细胞的凋亡起非常重要的调节作用.在许多研究中已经证实PI3K和Akt的抗凋亡时,Akt的表达水平增高并通过保护细胞免受凋亡而促进癌细胞的生长.现就PI3K/Akt信号通路的组成与功能、调节以及其抗恶性肿瘤细胞凋亡作用机理等方面的研究进展作一综述.     

磷脂酸肌醇-3-激酶/蛋白激酶B信号通路在肺部疾病中的作用研究进展

磷脂酸肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路是细胞内与增殖、分化和凋亡相关的信号通路，是机体自我保护的重要通路。PI3K被激活后会使其下游分子Akt磷酸化，进而抑制细胞凋亡、调控细胞生存及增殖。PI3K/Akt信号通路在众多肺系疾病，如急性肺损伤、肺炎、哮喘、肺纤维化、肺癌等的发展进程中起着重要作用。该文对PI3K/Akt信号通路在肺系疾病进展中的作用机制进行了综述。     

PD-1/PD-L1信号通路在黑色素瘤中的研究进展

细胞程序性死亡因子1(programmed death-1,PD-1)及其配体1(programmed death-ligand 1,PD-L1)是一对共刺激分子,激活细胞程序性死亡因子1及其配体1信号通路可抑制肿瘤特异性T细胞活性,有助于肿瘤细胞逃避免疫监视.而阻断该通路可以激活机体抗肿瘤免疫应答,抑制肿瘤细胞的生长...     

Nrf2/Keap1/ARE信号通路与难治性呼吸系统疾病研究进展

Nrf2/Keap1/ARE是重要的抗氧化信号通路,对维持体内抗氧化物与过氧化物平衡有重要作用。氧化应激发生时,Nrf2/Keap1/ARE信号通路被激活,调控下游抗氧化蛋白表达,减轻氧化应激对机体的损伤并减弱氧化应激的程度。近年来的研究发现,Nrf2/Keap1/ARE信号通路与肺纤维化、肺癌、慢性阻塞性肺病等难治性呼吸系统疾病的发生发展有密切联系,该通路可能作为治疗这类疾病的潜在靶点。该文就Nrf2/Keap1/ARE信号通路在难治性呼吸系统疾病中的作用进行综述,进一步了解其在难治性呼吸系统疾病中的作用机制,为这类疾病发病机制和治疗方案的研究提供可靠的参考。     

HGF/c-Met信号通路与肿瘤的关系及相关抗肿瘤药物的研究

综述肝细胞生长因子(HGF)及其受体c-Met的结构特征、HGF/c-Met信号通路的生物学作用及与细胞侵袭性生长和肿瘤转移的关系以及以此信号通路为靶点的抗肿瘤药物的研究进展。正常的HGF/c-Met信号通路在胚胎发育、器官形态以及血管发生等生理过程中发挥重要作用,而异常激活的该信号通路与肿瘤的演进和转移密切相关,极有望成为新的肿瘤治疗靶点。     

Notch信号通路调控Treg/Th17细胞机制的研究进展

摘要： Notch家族是多细胞生物发育过程中一类高度保守的、 十分重要的跨膜信号蛋白, 通过与相邻细胞之间的相互作用, 在细胞增殖、 分化、 凋亡中发挥着关键作用。调节性T细胞 （Treg） 及辅助性T细胞17 （Th17） 是目前发现的一类新型CD4+ T细胞亚群, 在生理状态下, 两者可通过分泌多种细胞因子来调节机体免疫的平衡。近年来, 越来越多的研究发现Notch信号通路通过调控Treg、 Th17细胞参与机体多种疾病的发生。本文就Notch信号通路在血液系统疾病、 自身免疫系统疾病等疾病中对Treg/Th17细胞调控机制的研究进展作一简要综述。     

APO2L/TRAIL: new insights in the treatment of autoimmune disorders

Apo2 Ligand/TNF Related Apoptosis-Inducing Ligand (Apo2L/TRAIL) is a cytokine that belongs to the TNF superfamilily that was described as capable of inducing apoptosis on tumor cells through activation of the extrinsic pathway in a Fas-independent manner. Besides this function, Apo2L/TRAIL, like other members of the TNF superfamily, has been shown to exert important functions in the immune system. Depending on their status of activation, Apo2L/TRAIL can be expressed by various cells of the immune system such as natural killer cells, T cells, dendritic cells and macrophages and has been implicated in distinct immunoeffector, immunoregulatory functions. Whit respect to pathological conditions, the Apo2L/TRAIL signaling pathway plays an important role in the response to infections, in immune surveillance against tumors, and in autoimmune disorders. Moreover, its implication in suppression of autoimmunity suggests that Apo2L/TRAIL has potential as therapeutic agent not only in cancer but also in autoimmune diseases. In fact, Apo2L/TRAIL-based therapies have been shown effective in various animal models of autoimmune disease. This review summarizes the current knowledge on the biology of Apo2L/TRAIL and its role in the immune system. Finally, patent applications, mainly related with the use of Apo2L/TRAIL as therapeutic agent in several autoimmune diseases, are also summarized.     

Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14

Previous studies have shown that baicalin,an active ingredient of the Chinese traditional medicine Huangqin,attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway,but how it affects this pathway is unknown.It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex.In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo.Exposure to LPS(1μg/mL)induced inflammatory responses in RAW264.7 cells,evidenced by marked increases in the expression of MHC II molecules and the secretion of NO and IL-6,and by activation of MyD88/NF-κB p65 signaling pathway,as well as the expression of CD14 and TLR4.These changes were dose-dependently attenuated by pretreatment baicalin(12.5–50μM),but not by baicalin post-treatment.In RAW264.7 cells without LPS stimulation,baicalin dose-dependently inhibit the protein and mRNA expression of CD14,but not TLR4.In RAW264.7 cells with CD14 knockdown,baicalin pretreatment did not prevent inflammatory responses and activation of MyD88/NF-κB p65 pathway induced by high concentrations(1000μg/mL)of LPS.Furthermore,baicalin pretreatment also inhibited the expression of CD14 and activation of MyD88/NF-κB p65 pathway in LPS-induced hepatocyte-derived HepG2 cells and intestinal epithelial-derived HT-29 cells.In mice with intraperitoneal injection of LPS and in DSS-induced UC mice,oral administration of baicalin exerted protective effects by inhibition of CD14 expression and inflammation.Taken together,we demonstrate that baicalin pretreatment prevents LPS-induced inflammation in RAW264.7 cells in CD14-dependent manner.This study supports the therapeutic use of baicalin in preventing the progression of LPS-induced inflammatory diseases.     

PI3K/AKT/mTOR信号通路参与自身免疫性

自身免疫性疾病（autoimmune disease，AD）是机体因自身抗原免疫耐受障碍而对自身抗原产生免疫反应，从而引起机体组织损伤的一类疾病。近年研究发现，磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶蛋白（phosphatidylin ositol 3-kinase/protein kinase B/mechanistic target of rapamycin kinase，PI3K/AKT/mTOR）信号通路与AD发病密切相关，其主要参与免疫细胞增殖分化、炎性细胞因子分泌、自噬及氧化应激等过程。本文重点概述PI3K/AKT/mTOR信号通路参与AD发病机理的研究进展。     

The regulation of CD4+ T cell immune responses toward Th2 cell development by prostaglandin E2

As an important immune mediator, PGE2 plays an important role in the immune tolerance, autoimmune diseases, immune regulation and tumor immunotolerance. PGE2 is considered to be a promising candidate for the control of the immune diseases. To further understand the immuno-modulating effects of PGE2 on CD4+ T cells, in vitro investigation was conducted in the present study. The results showed that PGE2 inhibited the proliferation of T cells in vitro in a dose-dependent manner. Gene expression profiling showed that 1716 genes were down regulated and 73 genes were up regulated with a change of 1.5 fold. Several signal transduction pathways were involved, such as TNF-α and NF-kB signaling pathway, T cell receptor signaling pathway, IL-2 signaling pathway, and MAPK pathway. The results showed that PGE2 inhibited IFN-γ, TNF-α and IL-4 production by CD4+ T cells 24 h after cell culture. A comparison between IFN-γ and IL-4 production showed that PGE2 enhanced the relative ratio of IL-4 to IFN-γ in CD4+ T cells culture, and regulated CD4+ T cells toward Th2 cell development. The results of the present study indicated that PGE2 has the potential to treat Th1-mediated inflammatory diseases by regulating CD4+ T cells toward Th2 cell immune response.     

Interleukin-2 as immunotherapeutic in the autoimmune diseases

Interleukins, also called cytokines are secretory proteins that bind to specific receptors and play a critical role in the intercellular communication between cells of the immune system. Cytokines are mainly produced by T lymphocytes, macrophages and eosinophils. Among its functions are the activation and suppression of immune system responses, induction of cell division and regulation of memory cells. Interleukin 2 (IL-2) is a secretory monomeric glycoprotein composed of 149 amino acids containing a signal peptide of 20 amino acids. It is classified as a member of the type I cytokines family. IL-2 binds to its receptor (IL-2R receptor) with high affinity and its signaling function promotes the activation of various subtypes of lymphocytes during the process of cell differentiation to generate an immune or homeostatic response. The specificity of IL-2 depends on its binding to low, medium or high-affinity receptors. Interleukin 2 acts as a regulator of the proliferation of CD4+ and CD8+ T cells. There is a relationship between IL-2 and autoimmune diseases due to its influence in the differentiation of T helper cells, which in turn directly influence immunological response processes. Therefore, IL-2 is a key element in the control and treatment of those diseases. In recent years, many therapeutic agents based on biomolecules and recombinant chimeric proteins have been developed to treat different autoimmune diseases. In this review, we focus on the use of interleukin 2 as a versatile therapeutic agent, alone or associated with other molecules to increase the efficiency of autoimmune disease treatment.     

Microglial activation and its implications in the brain diseases

An inflammatory process in the central nervous system (CNS) is believed to play an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, prion diseases, multiple sclerosis and HIV-dementia. The inflammatory response is mediated by the activated microglia, the resident immune cells of the CNS, which normally respond to neuronal damage and remove the damaged cells by phagocytosis. Activation of microglia is a hallmark of brain pathology. However, it remains controversial whether microglial cells have beneficial or detrimental functions in various neuropathological conditions. The chronic activation of microglia may in turn cause neuronal damage through the release of potentially cytotoxic molecules such as proinflammatory cytokines, reactive oxygen intermediates, proteinases and complement proteins. Therefore, suppression of microglia-mediated inflammation has been considered as an important strategy in neurodegenerative disease therapy. Several anti-inflammatory drugs of various chemical ingredients have been shown to repress the microglial activation and to exert neuroprotective effects in the CNS following different types of injuries. However, the molecular mechanisms by which these effects occur remain unclear. In recent years, several research groups including ours have attempted to explain the potential mechanisms and signaling pathways for the repressive effect of various drugs, on activation of microglial cells in CNS injury. We provide here a comprehensive review of recent findings of mechanisms and signaling pathways by which microglial cells are activated in CNS inflammatory diseases. This review article further summarizes the role of microglial cells in neurodegenerative diseases and various forms of potential therapeutic options to inhibit the microglial activation which amplifies the inflammation-related neuronal injury in neurodegenerative diseases.