CD247与免疫相关疾病的研究进展

肿瘤和自身免疫性疾病是当前的研究热点,其中免疫分子在疾病发生发展中起到了重要的作用。研究发现CD247分子在慢性炎症、自身免疫性疾病和肿瘤发展过程中发挥重要作用。CD247的表达和功能改变与T淋巴细胞异常活化相关,CD247基因表达水平的降低使TCR信号转导及细胞内信号转换异常,导致T淋巴细胞活化异常,进而引起免疫功能的缺失,导致慢性感染、免疫性疾病以及肿瘤的发生。CD247在免疫系统疾病及肿瘤组织中异常表达,可用于疾病监控、疗效评价、预后及复发的预测。     

自身抗体检测在风湿免疫性疾病诊治中的作用

风湿免疫性疾病是指由于多种原因使体内免疫功能紊乱而引起的疾病, 发病机制复杂且发病率高, 易反复发作。自身免疫耐受机制失调会产生多种针对自身细胞、组织及器官的自身抗体。目前已发现越来越多的风湿免疫性疾病相关自身抗体与临床表现、疾病过程、临床并发症及预后存在关联。总结自身抗体的临床意义对风湿免疫性疾病的早期诊断、病情活动度评估、预后判断尤为重要。     

趋化因子配体18(CCL-18)在白血病患者中的表达及其意义

趋化因子能够招募单核细胞、中性粒细胞、淋巴细胞等各种免疫细胞聚集至病原体入侵的部位,在免疫反应中发挥关键作用.趋化因子配体18 (CCL-18)是主要由单核/巨噬细胞和树突状细胞(DC)分泌的一种趋化因子,主要选择性趋化初始T细胞,与多种疾病有关,在变态反应及自身免疫性疾病中的作用报道较多[1],随着肿瘤学的发展,关于CCL-18在恶性肿瘤中的研究报道也越来越多,如在乳腺癌、胃癌及卵巢癌等许多实体瘤中CCL-18的水平升高[2],参与肿瘤的发病过程,现已成为上述肿瘤的一种检测指标.正是由于CCL-18与多种恶性肿瘤有关,而且其在血循环中持续存在,促使人们研究其在血液肿瘤中的作用.近几年研究发现其在白血病患者中有着较高的表达,并作为白血病的一种新的生物学指标,在鉴别诊断、判断预后中起重要作用.本文中主要就CCL-18的生物学性能、CCL-18在各种白血病中的表达及其意义作一综述.     

白细胞介素-21在疾病中作用的研究进展

白细胞介素-21(IL-21)是一种新近发现的细胞因子,具有广泛生物学活性,能够调节B细胞的分化及免疫球蛋白类别转换,促进T细胞、NK细胞的增殖、分化,提高NK细胞杀伤活性,是多种自身免疫性疾病、感染性疾病、变态反应性疾病和肿瘤的重要致病因素,在疾病的发生发展中举足轻重,具有潜在临床研究价值,可能成为多种疾病治疗的新靶标.作为新的免疫系统调节因子,IL-21在免疫性疾病中的作用越来越受到关注,已成为近年来研究的热点.     

单核细胞表面CD86分子的研究进展

共刺激分子在抗原递呈中起着重要的作用,CD86则是非常重要的共刺激分子,它与配体CD28和CTLA-4相结合后,能够产生重要的免疫学效应.CD86的升高和降低受多种因素影响.CD86的升高与降低在临床上也具有重要的意义,并且和疾病的预后相关.对于自身免疫性疾病而言,对CD86信号的调节,也提供了合理的有效的调节免疫系统的途径.     

免疫负调控因子TIPE2在自身免疫性疾病发病过程中的作用及机制研究进展

自身免疫性疾病是由于机体免疫系统对自身组织和器官发生了免疫应答并造成组织损伤和功能障碍的一类疾病,约占全世界人口的5％～10％.多种器官特异性自身免疫性疾病主要是由T细胞介导的,此外,其它的免疫细胞,如B细胞、T调节细胞、树突状细胞和巨噬细胞等在自身免疫性疾病的发生过程中也起着非常重要的作用.肿瘤坏死因子α诱导蛋白8-2(TNFAIP8L2或TIPE2)是2008年发现的免疫负调控因子,主要在免疫细胞中表达,通过对固有免疫和适应性免疫进行负性调控,从而维持体内环境稳定,实现免疫耐受.最近的研究发现,TIPE2在自身免疫性疾病的发病过程中起着非常重要的作用.     

长链非编码RNA在 疫应答中的研究进展

随着高通量测序的出现,人类基因组中证实存在一类没有蛋白编码功能、长度大于200个核苷酸的长链非编码RNA (lncRNA),经进一步的深入研究,发现其与肿瘤、心脑血管等疾病的发病密切相关.然而,lncRNA在免疫系统中的作用研究尚属一个新兴领域,近些年来的研究表明lncRNA亦参与了免疫调节的过程,在固有免疫和适应性免疫中发挥着不容忽视的作用.因此,对免疫系统中lncRNA功能的阐述将有助于理解各种免疫性疾病的发病机制.     

色氨酰tRNA合成酶(TTS)的免疫调节作用

近年来,在自身免疫性疾病、移植排斥和抗肿瘤免疫中,免疫系统的过度激活和免疫耐受逐渐成为研究关注的热点.大量研究证实,吲哚胺2,3双加氧酶(IDO)是催化色氨酸沿犬尿氨酸途径分解代谢的限速酶,其高表达在抑制T细胞免疫、诱导肿瘤免疫耐受中发挥重要的调节作用[1-2].研究显示,另一种色氨酸代谢酶——色氨酰tRNA合成酶(tryptophanyl-tRNA synthetase,TTS,TrpRS)能够催化色氨酸与其对应的tRNA结合,增加细胞内色氨酰tRNA储备,对抗IDO介导的色氨酸消耗,参与机体的免疫调节过程,与多种自身免疫性疾病及恶性肿瘤的发生、发展和预后密切相关,但其具体的调控机制尚未完全阐明.现就TTS参与的色氨酸代谢过程及其免疫调节作用作一综述.     

cGAS-cGAMP-STING信号通路的功能及研究进展

cGAS-cGAMP-STING信号通路是固有免疫系统重要组成部分,通过识别胞浆DNA诱导I型干扰素(interferons,IFNs)和其他细胞因子产生,介导抗微生物先天免疫,同时也在肿瘤进展及远处转移中发挥作用。深入了解cGAS-cGAMP-STING信号通路与炎症性疾病、自身免疫性疾病及肿瘤发生发展的关系,以及S...     

B淋巴细胞与免疫老化

免疫老化(immunosenescence)是机体免疫系统随年龄增长而出现的退行性变化,免疫细胞是免疫系统的重要组成部分.其中B淋巴细胞既是机体产生抗体的惟一细胞,同时又是专职性的抗原提呈细胞.因此,B淋巴细胞在机体的细胞免疫及体液免疫中均发挥重要作用.研究发现,随着年龄的增长,B淋巴细胞的生成环境、数量及功能等均发生渐进性改变,从而导致机体正常免疫应答功能紊乱.致使年长者易罹患肿瘤、感染及自身免疫性等疾病.     

Matrix Metalloproteinase-9 and Autoimmune Diseases

Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.     

The roles and applications of autoantibodies in progression,diagnosis, treatment and prognosis of human malignant tumours

The existence of autoantibodies towards an individual's own proteins or nucleic acids has been established for more than 100 years, and for a long period, these autoantibodies have been believed to be closely associated with autoimmune diseases. However, in recent years, researchers have become more interested in the role and application of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Over the past few decades, numerous epidemiological studies have shown that the risk of certain cancers is significantly altered (increased or decreased) in patients with autoimmune diseases, which suggests that autoantibodies may play either promoting or suppressing roles in cancer progression. The idea that autoantibodies are directly involved in tumour progression gains special support by the findings that some antibodies secreted by a variety of cancer cells can promote their proliferation and metastasis. Because the cancer cells generate cell antigenic changes (neoantigens), which trigger the immune system to produce autoantibodies, serum autoantibodies against tumour-associated antigens have been established as a novel type of cancer biomarkers and have been extensively studied in different types of cancer. The autoantibodies as biomarkers in cancer diagnosis are not only more sensitive and specific than antigens, but also could appear before clinical evidences of the tumours, thus disclosing them. The observations that cancer risk is lower in patients with some autoimmune diseases suggest that certain autoantibodies may be protective from certain cancers. Moreover, the presence of autoantibodies in healthy individuals implies that it could be safe to employ autoantibodies to treat cancer. Of note, an autoantibodies derived from lupus murine model received much attention due to their selective cytotoxicity for malignant tumour cell without harming normal ones. These studies showed the therapeutic value of autoantibodies in cancer. In this review, we revisited the pathological or protective role of autoantibodies in cancer progression, summarize the application of autoantibodies in cancer diagnosis and prognosis, and discuss the value of autoantibodies in cancer therapy. The studies established to date suggest that autoantibodies not only regulate cancer progression but also promise to be valuable instruments in oncological diagnosis and therapy.     

Metabolic determinants of lupus pathogenesis

The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4⁺ T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues.     

Silicone implant incompatibility syndrome (SIIS): A frequent cause of ASIA (Shoenfeld’s syndrome)

Silicon has a molecular mass of 28 daltons. In nature, silicon is found as silicon dioxide (silica) or in a variety of silicates (e.g., in talc or asbestos). Furthermore, silicon is present in silicones, polymerized siloxanes, which are often used as medical silicones in breast implants. Silicon exposure is associated with different systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. Remarkably, silicon in silicone-filled breast implants is considered to be safe, not increasing the risk of developing autoimmune diseases. We analyzed the impact of silicone-filled breast implants on the immune system in 32 consecutive patients attending a specialized autoimmunity clinic. All 32 patients had silicone implant incompatibility syndrome and complaints fulfilling the diagnostic criteria of ASIA (autoimmune/inflammatory syndrome induced by adjuvants). Furthermore, in 17 of the 32 patients, a systemic autoimmune disease was diagnosed, and 15 of the 32 patients had an impaired humoral immune system. Patients developed symptoms and signs after long-term follow-up, suggesting that these symptoms and signs started after implant aging and/or rupture. We postulate that silicon in silicone-filled breast implants may increase the risk of developing (auto) immune diseases and immune deficiencies.     

Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis

In many models of organ-specific autoimmune diseases, mast cells provide a critical cellular link between autoantibodies and end-organ inflammation, both initiating and propagating disease. However, their role in systemic autoimmunity remains speculative. We therefore examined the role of mast cells in a murine model of systemic immune complex-related autoimmune disease, lupus nephritis, expecting to observe the development of humoral autoimmunity in the absence of end-organ disease. Surprisingly, not only did mast cell-deficient animals develop characteristic humoral features of lupus, including hypergammaglobulinemia and autoantibodies, they also developed immune complex glomerulonephritis, as evidenced by renal immune deposits, glomerular disease, and proteinuria. These findings implicate the presence of distinct effector pathways to end-organ damage in humoral autoimmune diseases: one involving the interaction between autoantibodies and mast cells to recruit inflammation in organ-specific autoimmunity, and another involving a more direct--mast cell-independent--interaction between autoantibodies and circulating inflammatory mediators in systemic autoimmunity.     

Immune responses to DNA in normal and aberrant immunity

Because of structural microheterogeneity, DNA can exert powerful effects that lead to immune system activation as well as antibody induction. These activating effects resemble those of endotoxin and result from sequences that occur much more commonly in bacterial DNA than in mammalian DNA. In contrast, mammalian DNA can inhibit the response to bacterial DNA as well as other stimuli and may serve a counterregulatory role during infection. The recognition of the immune effects of DNA is relevant to the pathogenesis of a variety of infectious and inflammatory diseases including systemic lupus erythematosus, a prototypic autoimmune disease characterized by anti-DNA autoantibodies.     

Epigenetics in human autoimmunity. Epigenetics in autoimmunity - DNA methylation in systemic lupus erythematosus and beyond

Epigenetic mechanisms are essential for normal development and function of the immune system. Similarly, a failure to maintain epigenetic homeostasis in the immune response due to factors including environmental influences, leads to aberrant gene expression, contributing to immune dysfunction and in some cases the development of autoimmunity in genetically predisposed individuals. This is exemplified by systemic lupus erythematosus, where environmentally induced epigenetic changes contribute to disease pathogenesis in those genetically predisposed. Similar interactions between genetically determined susceptibility and environmental factors are implicated in other systemic autoimmune diseases such as rheumatoid arthritis and scleroderma, as well as in organ specific autoimmunity. The skin is exposed to a wide variety of environmental agents, including UV radiation, and is prone to the development of autoimmune conditions such as atopic dermatitis, psoriasis and some forms of vitiligo, depending on environmental and genetic influences. Herein we review how disruption of epigenetic mechanisms can alter immune function using lupus as an example, and summarize how similar mechanisms may contribute to other human autoimmune rheumatic and skin diseases.     

Engineering vaccines and niches for immune modulation

Controlled modulation of immune response, especially the balance between immunostimulatory and immunosuppressive responses, is critical for a variety of clinical applications, including immunotherapies against cancer and infectious diseases, treatment of autoimmune disorders, transplant surgeries, regenerative medicine, prosthetic implants, etc. Our ability to precisely modify both innate and adaptive immune responses could provide new therapeutic directions in a variety of diseases. In the context of vaccines and immunotherapies, the interplay between antigen-presenting cells (e.g. dendritic cells and macrophages), B cells, T helper and killer subtypes, and regulatory T- and B-cell responses is critical for generating effective immunity against cancer, infectious diseases and autoimmune diseases. In recent years, immunoengineering has emerged as a new field that uses quantitative engineering tools to understand molecular-, cellular- and system-level interactions of the immune system and to develop design-driven approaches to control and modulate immune responses. Biomaterials are an integral part of this engineering toolbox and can exploit the intrinsic biological and mechanical cues of the immune system to directly modulate and train immune cells and direct their response to a particular phenotype. A large body of literature exists on strategies to evade or suppress the immune response in implants, transplantation and regenerative medicine. This review specifically focuses on the use of biomaterials for immunostimulation and controlled modulation, especially in the context of vaccines and immunotherapies against cancer, infectious diseases and autoimmune disorders. Bioengineering smart systems that can simultaneously deliver multiple bioactive agents in a controlled manner or can work as a niche for in situ priming and modulation of the immune system could significantly enhance the efficacy of next-generation immunotherapeutics. In this review, we describe our perspective on the important design aspects for the development of biomaterials that can actively modulate immune responses by stimulating receptor complexes and cells, and delivering multiple immunomodulatory biomolecules.     

组蛋白修饰在自身免疫性疾病中的作用

组蛋白修饰是表观遗传修饰的重要方式,在基因表达的调控中扮演重要角色.常见的组蛋白修饰包括组蛋白乙酰化和甲基化.自身免疫性疾病是以机体对自身抗原发生免疫应答而导致自身组织损害为特点的一类疾病.有研究证实,组蛋白修饰参与了多种自身免疫性疾病的发生和发展,如系统性红斑狼疮、类风湿性关节炎、系统性硬化.因而阐明组蛋白修饰的机制可为自身免疫性疾病的治疗提供新的思路.     

SOCS signaling in autoimmune diseases: Molecular mechanisms and therapeutic implications

Suppressor of cytokine signaling (SOCS) proteins are mainly induced by various cytokines and have been described as classical inhibitors of cytokine signaling. SOCS signaling is involved in the regulation of immune cells, and recent findings suggest that SOCS proteins, especially SOCS1 and SOCS3, are often dysregulated in a wide variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, psoriasis, and multiple sclerosis. Recent studies suggest that SOCS signaling could be therapeutically targeted in various autoimmune diseases. In this review, we discuss recent studies on the role of SOCS proteins in the development and pathogenesis of autoimmune diseases, as well as their clinical implications.