核受体家族4A(NR4A)与免疫细胞及相关疾病关系的研究进展

核受体家族4A(NR4A)是核受体亚家族成员,其转录活性很大程度上由其表达水平决定。NR4A参与多种信号转导通路,如核因子κB(NF-κB)通路等,调控相关靶基因的表达,在T淋巴细胞、造血干细胞、单核细胞、巨噬细胞、调节性T细胞(Treg)等免疫细胞的分化、发育中发挥重要作用。它还参与机体自身免疫耐受及免疫自稳态的形成,可以通过调节免疫细胞极化作用控制机体炎症应答的强度。NR4A基因缺失可以导致严重的自身免疫反应。此外,NR4A受体在机体代谢、免疫功能、心血管疾病、神经系统功能、炎症性疾病、恶性肿瘤中扮演重要角色。     

核受体参与调控细胞自噬的研究进展

核受体是一种转录调节因子,参与细胞生长、分化、凋亡、物质代谢及肿瘤形成等几乎所有的生物学过程,并可受与其结合的小分子调控。自噬是一种特殊的程序性细胞死亡方式,是高度保守的代谢过程,一旦发生自噬缺陷或自噬过量都会引起相应疾病的发生发展。近年来,众多研究表明核受体与自噬相关。因此,本文主要综述核受体参与调控细胞自噬的研究进展,着重介绍几种核受体参与细胞自噬调控的机制研究,以期了解核受体参于调节细胞自噬的分子基础,为治疗相应疾病提供可能的思路及治疗策略。     

多不饱和脂肪酸对基因表达的调控机制

多不饱和脂肪酸(PVFAs)不仅是细胞结构和功能的重要组成成分,而且对细胞生长、代谢、分化中的基因起调控作用。研究表明PUFAs可通过与肝脏核因子-4α、肝脏X受体α,β、过氧化物酶体增殖物激活受体(PPARs)等核受体直接作用,或与转录因子固醇调节元件结合蛋白1,2间接作用,以多种机制在分子水平上调节相关酶的基因转录。深化PUFAs基因调控机制的研究,对于营养、健康和医疗具有重要意义。     

模式识别受体NLRC3的生物学效应及在免疫相关疾病中的研究进展

固有免疫系统是宿主抵御病原微生物攻击的第一道防线。可以快速识别并产生免疫反应，清除致病微生物。然而，强烈的免疫反应可能会导致过度炎症，甚至自身免疫性疾病。含胱天蛋白酶活化和募集结构域核苷酸结合寡聚结构域样受体3(NLRC3)位于细胞质中，是固有免疫系统的重要负调节因子，可以抑制体内过度的免疫反应。NLRC3既能够通过影响核因子κB(NF-κB)和干扰素基因刺激因子(STING)相关信号通路，减少促炎细胞因子的产生；还能通过干扰含pyrin结构域核苷酸结合寡聚结构域样受体家族蛋白3(NLRP3)炎性体复合体的组装和活性来抑制炎症反应。此外，还可以通过调控磷脂酰肌醇激酶3/哺乳动物雷帕霉素靶蛋白(PI3K/mTOR)等通路影响细胞的代谢、增殖、凋亡等生物学行为。NLRC3对细胞功能的这些调控作用，与感染性疾病、自身免疫性疾病和肿瘤等多种免疫相关性疾病的发生发展密切相关，通过调控NLRC3的表达可能成为治疗这些疾病的一个有效途径。     

核转录因子—κB与免疫应答

核转录因子-κB(nuclear factor κB，NF—κB)是一种重要的核转录因子，NF-κB系统由NF-κB／Rel蛋白家族和IκB蛋白家族组成，通过对多种基因表达的调节，影响机体非特异性免疫反应和特异性免疫反应，从而在体机免疫功能调节中发挥重要作用。本文就NF-κB在免疫应答中的作用作一综述。     

代谢免疫学:新兴的前沿

代谢和免疫是机体生存最基本的需求。在长期的进化过程中,各种生物都形成了代谢和免疫反应的共同通路。因此,免疫反应和代谢调节高度统一,功能上相互依赖,这种免疫和代谢之间的相互作用可以被看作机体稳态调节的核心机制。代谢免疫学就在代谢和免疫相互联系的基础上研究免疫与代谢之间相互作用的途径、模式及其调控的一门新兴学科,并在此基础上更好地了解相关疾病的病理机制,探讨新的治疗方法。代谢免疫学的全新时代正在到来。     

PPAR-γ在免疫中的调节作用

过氧化物酶体增殖激活受体γ(PPAR-γ)是核激素受体PPAR的一种亚型,PPAR-γ在糖脂合成与代谢以及免疫内环境稳定中发挥重要作用.随着对PPAR-γ研究日益深入,人们发现其与细胞分化、凋亡、免疫细胞增殖和细胞因子分泌调控均密切相关,在自身免疫性疾病、炎症反应、超敏反应、移植免疫及先天性免疫中发挥重要的作用.     

代谢性核受体及其与代谢综合征的关系

代谢性核受体是一组与代谢调节相关的配体激活核受体转录因子,主要包括脂质过氧化物体增殖物激活受体(PPARs)、肝X受体(LXRs)和法尼酯衍生物X受体(FXRs)3种。它们在胰岛素敏感性、脂肪生成、脂质代谢、能量代谢、血压调节、炎症、细胞生长和分化等过程中起着关键的调节作用,因而近年来倍受关注。越来越多的研究表明这3种核受体不仅与代谢综合征,包括胰岛素抵抗、糖耐量受损2、型糖尿病、肥胖、高脂血症、高血压和微白蛋白尿之间存在密切的关系,也在动脉粥样硬化的发生及发展中有重要的作用。本文就代谢性核受体的生物学活性和生理功能作一简述,并对其在代谢综合征发病机制中的作用进行重点讨论。     

孤核受体RORα的研究进展

孤核受体RORα作为核受体超家族成员，广泛分布于机体各组织，近年来国外学者对结构、功能做了大量研究，不断发现其通过对目的基因转录调控，在许多重要生理活动发挥重要的调节功能，在对抗心血管疾病、慢性炎症、免疫功能不全、骨代谢障碍、肿瘤等一些病理过程中发挥重要作用。     

TrkA、TrkB和TrkC受体在大鼠三叉神经本体觉中枢通路上的表达

目的 检查高亲和性的神经营养物质受体(TrkA、TrkB和TrkC)在大鼠三叉神经本体觉中枢四级通路上的分布。方法 采用免疫组织化学的抗生物素．生物素一过氧化物酶复合物(ABC)方法并以二氨基联苯胺(DAB)为呈色剂，检查免疫反应细胞。结果 3种受体在三叉神经本体觉中枢四级通路的三叉神经中脑核、二级和三级核团均有表达。同一核团内3种受体的免疫阳性细胞密度不同。在胞体和突起上均观察到TrkA和TrkB免疫反应染色，但TrkB标记的突起较长，TrkC染色多局限于细胞体部分。结论 在三叉神经本体觉中枢通路中，3种神经营养物质受体都可能在维持神经元存活和调节递质释放等方面发挥特定的作用。     

Open system gene expression profiling and identification of novel genes for targeted vaccine delivery

Ongoing development of vaccines is limited by the techniques used to identify routes to immunization. Using open system gene expression profiling, researchers can now directly identify receptors used by M-cells in the transport of antigens to the mucosal immune system. These receptors will be ideal for targeted delivery of new synthetic vaccines. In addition, gene expression profiling will provide important new information on the biology of the M-cell and mucosal immune mechanisms.     

Frienemies of infection: A chronic case of host nuclear receptors acting as cohorts or combatants of infection

Abstract

Macrophages and dendritic cells provide critical effector functions to efficiently resist and promptly eliminate infection. Pattern recognition receptors signaling operative in these cell types is imperative for their innate properties. However, it is now emerging that besides these conventional signaling pathways, nuclear receptors coupled gene regulation and transrepression pathways assemble immune regulatory networks. A couple of these networks associated with members of nuclear receptor superfamily decide heterogeneity in macrophages and dendritic cells population and thereby play decisive role in determining protective immunity against bacteria, viruses, fungi, protozoa and helminths. Pathogens also direct shift in the expression of nuclear receptors and their target genes and this is proclaimed to be a sui generis mechanism whereby microbes disconnect the genomic component from the peripheral immune response. Many endogenous and synthetic nuclear receptor ligands have been tested in various in vitro and in vivo infection models to study their effect on pathogen burden. Here, we discuss current advances in our understanding of the composite interactions between nuclear receptor and pathogens and their implications on the causatum infectious diseases.     

The Toll-receptor family and control of innate immunity

Innate immune recognition is mediated by a system of germline-encoded receptors that recognize conserved molecular patterns that are associated with microbial pathogens. These receptors are coupled to signal transduction pathways that control expression of a variety of inducible immune-response genes. Toll receptors and the associated signaling pathways of nuclear factor kappaB may represent the most ancient host defense system found in mammals, insects and plants.     

Toll-like receptors and the eye

PURPOSE OF REVIEW: This review will describe the structure, expression/distribution and functional activity of Toll-like receptors, in particular in the ocular structures. It will also discuss innate and adaptive immune responses, by exploring the possible modulation/regulation of innate and adaptive immunity by Toll-like receptors, in view of recent findings observed in the ocular surface. RECENT FINDINGS: Current knowledge indicates that Toll-like receptors represent essential elements in host defence against pathogens, a prerequisite to the induction of adaptive immune responses. The expression/distribution of Toll-like receptors in the healthy eye highlights the possible function of Toll-like receptors in both innate and adaptive responses during pathological conditions of the ocular surface. SUMMARY: Recent findings have greatly increased the knowledge of the possible role of Toll-like receptors in innate and adaptive immune responses. Toll-like receptors seem to play different roles in a wide range of activities of the immune system, and might represent an exclusive link between innate and adaptive responses under pathological conditions. Recent studies in ophthalmology have highlighted the role of Toll-like receptors in infections (keratitis) as well as in allergic states of the ocular surface. This review thus describes the relationship between Toll-like receptors and the main immune/structural cells taking part in inflammatory disorders. Understanding the complex mechanisms underlying Toll-like receptor localization and function will provide additional data that might help devise novel therapeutic approaches involving Toll-like receptors and their agonists, in an attempt to modulate the biased immune system.     

The roles of orphan nuclear receptors in the development and function of the immune system

Hormones and their receptors regulate cell growth,differentiation and apoptosis and also play important rolesin immune function.Recent studies on the subfamily of the orphan nuclear receptors known as retinoid-acidrelated orphan receptors (ROR) have shed important insights on the roles of this group of nuclear proteins inthe development and function of the immune system.RORα regulates inflammatory cytokine production inboth innate and adaptive immune system while RORγ regulates the normal development of T lymphocyterepertoire and secondary lymphoid organs.Cellular & Molecular Immunology.2004;1(6):401-407.     

Innate immunity in allergy

Innate immune system quickly responds to invasion of microbes and foreign substances through the extracellular and intracellular sensing receptors, which recognize distinctive molecular and structural patterns. The recognition of innate immune receptors leads to the induction of inflammatory and adaptive immune responses by activating downstream signaling pathways. Allergy is an immune‐related disease and results from a hypersensitive immune response to harmless substances in the environment. However, less is known about the activation of innate immunity during exposure to allergens. New insights into the innate immune system by sensors and their signaling cascades provide us with more important clues and a framework for understanding allergy disorders. In this review, we will focus on recent advances in the innate immune sensing system.