树突细胞与哮喘Th1/Th2失衡

特应性哮喘患者以Th2免疫反应为主,导致气道炎症,Th1／Th2失衡是特庆性哮喘重要的免疫病理机制,树突细胞（DCs）中肺部主要抗原递呈细胞,不但可以介志对吸入抗原初始的免疫反应,活化辅助性T细胞,而且在可以决定T细胞的分化方向,维持哮喘Th2免疫反应和Th1／Th2失衡机制中发挥重要作用而日益受到重视。本文就近年来对特应性哮喘免疫病理机制中DCs对Th1／Th2失衡影响认识作一综述。     

胸腺基质淋巴生成素对树突状细胞的活化作用及其在Th2型炎症中的意义

树突状细胞(dendritic cells, DCs)是体内最重要的抗原提呈细胞,其对外源性抗原的高效的加工、处理和提呈是启动T细胞应答的关键步骤;同时DCs又是免疫应答的重要调节者,不同微环境中的DCs受不同因子的作用而发生不同的成熟活化过程,从而诱导机体产生针对该环境所需要的不同的免疫应答.胸腺基质淋巴生成素(Thymic stromal lymphopoietin,TSLP)是一类优先表达于肺、肠、皮肤等上皮细胞的细胞因子,尤其在超敏反应性炎症部位表达极高.TSLP对DCs具有重要调控作用,可促进DCs的活化、成熟,增强其对CD4 T细胞的活化能力,并促使Th0细胞向Th2分化,在特应性皮炎、哮喘等炎症发生中具有重要意义.     

Th17细胞与Th1细胞在慢性阻塞性肺疾病炎症发病机制中的调控作用

慢性阻塞性肺疾病(COPD)发病的分子机制目前仍不甚清楚,大量证据表明,T淋巴细胞介导的免疫反应贯穿于COPD的各个阶段,导致炎症反应持续放大.近来研究发现,Th1细胞和Th17细胞均参与了COPD的免疫发病过程,通过相互间作用调控COPD的炎症反应.因此,深入了解COPD炎症发病过程中Th17、Th1细胞免疫应答特征、分化及调控功能,对探讨COPD的致病机制以及免疫调节治疗的靶点具有重要意义.     

大鼠未成熟树突状细胞体外分离、扩增与鉴定

树突状细胞(Dendritic cells,DCs)是目前为止发现的功能最强的专职抗原提呈细胞,而不同生长阶段的DCs对于诱导T细胞免疫应答的能力也有所不同,未成熟树突状细胞(immature dendritic cells,iDCs)具有极强的抗原摄取能力,并能诱导T细胞的免疫耐受[1].为进一步研究iDCs诱导免疫耐受的功能及特性,我们建立了利用大鼠骨髓细胞诱导产生iDCs,并对其表型和功能进行分析鉴定.     

间充质干细胞调节树突状细胞相关功能的研究进展

树突状细胞(DCs)作为体内最强大的抗原提呈细胞,是适应性免疫应答的始动者,在较多疾病的发生发展过程中起着重要作用.间充质干细胞(MSCs)是具有多向分化潜能的成体干细胞,由于其强大的自我修复、抑制炎症以及免疫调节作用已成为研究的热点.大量的研究表明MSCs能通过影响DCs的成熟及功能,达到缓解疾病的目的.通过对MSCs调节DCs功能调节的深入研究有望取得疾病治疗的新进展.     

树突状细胞对调节性T细胞的调控作用

树突状细胞(DCs)是目前已知的体内功能最强大的专职性抗原提呈细胞,具有启动免疫应答和诱导免疫耐受的双重特性.近年来树突状细胞对调节性T细胞的调控作用是免疫学领域的一个研究热点.Foxp3+ Tregs是一群同时具有免疫低反应性和免疫抑制性功能两大特征的T淋巴细胞,它在维持机体内环境稳定、预防自身免疫性疾病、抑制移植排斥反应等病理生理过程中发挥着重要作用.越来越多的研究结果证实DCs和Tregs二者在维持外周免疫耐受中存在着紧密联系,DCs可以诱导抗原特异性Tregs的生成并增加后者的抑制活性,其中参与该调节机制的分子主要包括相关细胞因子、Toll样受体、共刺激分子及维甲酸等.对DCs在接触共生和致病微生物时诱导和调控Tregs细胞有了一些新发现.     

树突状细胞对Th17/Treg免疫平衡调节的研究进展

树突状细胞(dendritic cells,DCs)对辅助性T细胞17(T help cell 17,Th17)/调节性T细胞(regulatory T cell,Treg)平衡的调控是免疫学研究中目前最为活跃的研究领域之一.Treg和新近发现的Th17是机体存在的两种不同于Th1和Th2的CD4+T细胞新亚型.Th17细胞介导炎症、延续破坏进程,Treg细胞对抗炎症、维持免疫耐受.机体处于正常状态下二者保持平衡,但新近研究发现,在自身免疫性疾病、感染、肿瘤等诸多疾病中存在Th17/Treg细胞失衡,进而诱导异常免疫应答,导致多种免疫性疾病的发生.作为机体功能最强的专职抗原提呈细胞(antigen-presenting cells,APC) ——DCs对Th17/Treg细胞平衡如何发挥着调控作用备受关注,本文将对其研究进展予以综述.     

树突状细胞引流淋巴结归巢的研究进展

树突状细胞(dendritic cells,DCs)是目前已知的体内功能最强的专职性抗原提呈细胞(professional antigen-present-ing cells,pAPC),在引发和调节机体的免疫反应中起着重要作用。树突状细胞最重要的功能是摄取、加工处理、提呈抗原,并刺激初始T细胞(naive T cells)活化、增殖,从而激发机体的免疫应答。DCs这一功能是在体内迁移过程中发挥的,其中DCs归巢至引流淋巴结被认为是激发免疫应答的关键步骤之一。本文将就近年来DCs归巢至引流淋巴结的研究进展作一综述。     

树突状细胞在调节性T细胞产生中的作用

树突状细胞（Dendritic cells，DCs）是一类重要的专职抗原提呈细胞，虽在体内的数量较少，但具有超强的抗原提呈能力，而且能够活化初始T细胞（Naive T cells），在免疫应答的诱导中具有独特的地位。DCs既能诱导有效的免疫应答，同时在诱导免疫耐受中也十分重要。在中枢耐受中，胸腺内的DCs可以通过阴性选择清除自身反应性T细胞。近年来，越来越多的证据表明，DCs在外周耐受中也起着关键性的作用，可以通过诱导效应性CD4^＋T或者CD8^＋T细胞的无能，促进调节性T细胞（T regulatory cells，Treg）的分化来调控针对自身抗原的外周耐受。DCs的来源、表型和成熟状态都具有多样性和异质性，DCs的耐受功能可能依赖于其某一成熟阶段或者是某一亚群。本文就DCs在诱导产生Treg中的作用和应用进展做一简要综述。     

树突状细胞诱导Th17细胞分化及其在气道炎症性反应中的作用

树突状细胞(DCs)是最具潜能的抗原提呈细胞,它能激活初始型T细胞并分泌相关细胞因子促进Th0的不同分化方向,在启动免疫应答中扮演着重要角色。Th17细胞是最新发现的与Th1、Th2不同的Th细胞亚群,能介导气道前炎症反应,并且与自身免疫病有关。本文综述了DCs诱导Th0向Th17细胞的分化研究及其在气道炎症性反应中的作用。     

Imbalance of circulating dendritic cell subsets in chronic obstructive pulmonary disease

Dendritic cells (DCs) play an unsettled role in chronic obstructive pulmonary disease (COPD) pathogenesis. Two main blood subsets, myeloid (m) and plasmacytoid (p) DCs, have been identified in humans. Phenotype and frequency of circulating DC subsets were assessed by multi-parametric flow cytometry in 28 COPD patients and 30 healthy controls (15 never smokers and 15 smokers). Proportion and absolute number of pDCs were significantly reduced in COPD patients in comparison with never smokers (p < 0.001 and p < 0.003) along with a marked increase of the mDC/pDC ratio (p < 0.001). Analysis of peripheral lymphocyte subsets showed that the naive/memory T cell ratio was significantly reduced in COPD patients in comparison with never smokers (p < 0.001). Similar perturbations in the distribution of DCs and T cells also occurred in control smokers. This study is the first report of an imbalance of blood DCs in COPD. Influence of smoking and clinical relevance of these findings are discussed.     

The role of Th1/Th2 cytokines played in regulation of specific CD4 + Th1 cell conversion and activation during inflammatory reaction of chronic obstructive pulmonary disease

CD 4 ⁺ Th1‐CXCR 3 signalling pathway may play a key role in chronic obstructive pulmonary disease (COPD ). The aim of this study was to explore Th1/Th2 cytokines ratio differences in patients in different stages of COPD and to confirm the hypothesis that elastin exposure might serve as an antigen to initiate the stimulation of CD 4 ⁺ Th1‐CXCR 3 immune inflammation pathway. Patients of COPD in different stages and normal individuals were enrolled. Ten millilitres of peripheral blood was drawn from patients. The concentration of CXCR 3, IFN ‐γ, IL ‐2, IL ‐4 and IL ‐13 in plasma was detected by ELISA . The Naïve CD 4⁺T cells were isolated from the peripheral blood mononuclear cells, which were stimulated by elastin and collagen before determining the level of IFN ‐γ secretion by ELISPOT . Compared with control group, the concentration of CXCR 3 in the acute exacerbation COPD (AECOPD ) group was higher (P  < .05). The concentration of IFN ‐γ and IL ‐2 in AECOPD group was lower than that in remission (P  < .05). The concentration of IFN ‐γ in the AECOPD and remission was higher than that in controls (P  < .05), while IL ‐2 was opposite (P  < .01). The concentration of IL ‐4 and IL ‐13 in AECOPD group was higher than that in the controls (P  < .05). The CD 4⁺Th1 cells stimulated by the elastin as antigen secreted more IFN ‐γ than that by collagen (P  < .01). CXCR 3 was highly expressed in patients with COPD . There were different Th1/Th2 cytokines in different stages of COPD . The CD 4+Th1‐specific conversion and activation may be an initiator of COPD immune inflammatory response.

     

Dendritic cell functions: Learning from microbial evasion strategies

Dendritic cells (DCs) are specialized antigen presenting cells (APC) that are fundamental to initiate both immunity and tolerance. DCs play a ‘sentinel’ role to protect our body from potential pathogens and induce tolerogenic responses toward harmless antigens. The flexibility of DCs or macrophages to adapt to the environment and to respond accordingly can be hijacked by pathogens for their own interest to transform a potentially immunogenic APC into a tolerogenic cell with clear consequences in pathogen clearance. While these immune evasion mechanisms can be detrimental for the host, they can highlight important molecular pathways in DCs necessary for their function. In this review we will mention several mechanisms employed by pathogens to evade DC patrolling function.     

碳纳米管对树突状细胞成熟和T细胞分化作用研究

Th分化在免疫应答过程中起着关键性的作用,主要由树突状细胞来调控。碳纳米管是由碳元素组成的空心管状纳米材料,可作为抗原载体。碳纳米管对树突状细胞和Th分化的影响是决定其免疫响应的关键因素。分析氧化多壁碳纳米管(CNT)对小鼠骨髓来源的树突状细胞(BMDCs)功能的影响,以及对过敏抗原多肽OVA_323-339的 Th1和Th2免疫反应的影响。实验结果显示,BMDCs大量吞噬CNT,但对其细胞表面活化标志分子CD86、MHCII以及细胞因子TNF-α表达没有明显变化。CNT/抗原复合物可促进BMDCs表面MHCII的表达和CD8⁺T细胞增殖,增殖细胞的比例由28.7%分别增加到40.6%、41.3%和29.6%。Th2型细胞因子IL-4、IL-13和IL-10的表达和CD4⁺T的增殖受到抑制,增殖细胞的比例由54.4%减少到38.9%、46.6%和39.8%。研究结果提示,CNT不影响DCs的成熟和活化,但CNT可以影响过敏抗原的Th分化平衡,可抑制Th2型细胞因子的表达,促进Th1型免疫响应。     

An update on the role of human dendritic cells in patients with atopic dermatitis

Dendritic cells (DCs) are without a doubt important key skin cells that connect information from the environment with the innate and adaptive immune system. Their function is decisive for the initiation and inhibition of immune responses, and therefore they play a central role for both the healthy and diseased states of the skin. The type, maturation stage, and function of DCs, as well as the micromilieu in which they are located and their contact with cellular partners in the surrounding area, are important cofactors that direct maintenance of immune homeostasis or breakout of inflammatory reactions in patients with chronic inflammatory skin diseases, such as atopic dermatitis. Thus better knowledge about the exact proinflammatory and anti-inflammatory properties of DCs in patients with atopic dermatitis and the disease-specific roles of DC subtypes would allow us to target these important immune cells with versatile functions for therapeutic purpose.     

The role of elastin peptides in modulating the immune response in aging and age-related diseases

It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.     

The role of dendritic cells in neuroblastoma: Implications for immunotherapy

Neuroblastoma is a solid tumor, which is originated from some neural tissues. The immune system including the innate and adaptive immune system fights against this tumor. Dendritic cells (DCs) play an important role in this way by recognizing tumor antigens and activating specific types of T cells. These cells are derived from monocytes that are induced by inflammatory factors secreted by different cells in the tumor microenvironment (TME). There are different types of DCs, including monocyte-derived DCs (moDC), plasmacytoid DCs (pDC), conventional DCs type 1 and 2 (cDC1 and cDC2), and Langerhans cells. DCs connect the innate and the adaptive part of the immune system and have an important role in anti-tumor immunity. There are some vaccines that involve specific types of DCs, which can be used to prevent neuroblastoma. Also, we can use the combination of inflammatory factors and DCs as a substitute for chemotherapy.     

Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus

Dendritic cells (DCs) constitute a heterogeneous population of professional antigen presenting cells which are the initiators and key regulators for both immunity and tolerance induction. The significance and impact of DC biology in contemporary immunology and medical research is heightened by the award of the 2011 Nobel Prize for Medicine and Physiology to Ralf Steinman for his discovery and subsequent work on the role of DC in adaptive immunity. As a central regulator of immune responses, DCs also play a pivotal role in the pathogenesis of chronic inflammatory autoimmune conditions such as systemic lupus erythematosus (SLE). In this review, we will focus on the respective role of the two major subsets of blood DC, namely myeloid (m)-DC and plasmacytoid (p)-DC, in SLE immunopathogenesis. Accumulating evidence has highlighted pDCs as the culprit for SLE pathogenesis, mainly through type-I interferon production. Latest findings in the field also decipher the mechanisms by which pDCs interact with neutrophils and platelets and contribute to SLE development. The recent surge of interest in studying microRNA regulation in SLE pathogenesis will also be discussed.     

Artificial human antigen‐presenting cells are superior to dendritic cells at inducing cytotoxic T‐cell responses

Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T‐cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I–peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T‐cell response, we generated artificial antigen‐presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic‐co‐glycolic) acid nanoparticles (PLGA‐NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen‐specific CTLs were then induced using either peptide‐loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen‐specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA‐A2‐positive tumour antigen‐bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA‐NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.