T-bet和Eomes对细胞免疫功能的调控作用

T-box expressed in T cells(T-bet)和Eomesodermin(Eomes)是调控I型效应T细胞的重要转录因子,对CD4I型辅助T细胞(Th1细胞)、NK细胞、CD8+细胞毒T淋巴细胞(CTL)等的分化发育和功能调控有重要作用。机体的抗肿瘤免疫主要依赖T淋巴细胞介导的适应性免疫应答和NK细胞介导的固有免疫应答。T-bet和Eomes通过调控这些免疫细胞影响抗肿瘤免疫应答,对肿瘤的发生、发展及转归有重要意义。     

MDSC对免疫系统的抑制机制

机体的免疫系统是一个复杂的网络调控系统,由固有免疫和适应性免疫组成,其中包括了固有免疫细胞、抗原递呈细胞、适应性免疫细胞等之间的相助作用和调节。越来越多的证据表明一群骨髓来源的具有CD11b和Gr-1标志的抑制性细胞在各种感染、肿瘤、急慢性炎症等疾病中大量存在,并且负向调节机体的免疫功能。这就是具有负向调节机体免疫反应的髓系抑制性细胞(MDSC),近年来被广泛研究。MDSC是免疫系统调节机体免疫反应的一群独特的细胞群体,可以对多种免疫细胞通过多种不同的机制发挥免疫抑制功能,从而导致机体固有免疫和适应性免疫功能的低下,促进疾病的发展和恶化。本文着重就MDSC对参与机体免疫反应的几种炎性细胞的抑制     

NK细胞在常见寄生虫病免疫中的研究进展

自然杀伤(NK)细胞作为机体固有免疫系统的重要效应细胞,在寄生虫感染免疫中的作用备受关注。我们主要总结了寄生虫感染后NK细胞数目稳态的变化、 NK细胞与其他实质细胞或免疫细胞之间的相互作用及细胞能动性改变、 NK细胞活化性和抑制性信号与细胞内部效应通路改变、细胞激活后细胞毒性功能改变、对其他免疫细胞功能和后续适应性免疫应答类型的影响等,关注NK细胞与寄生虫感染结局之间的关系以及其对相关疫苗效价的影响,以便全面地了解NK细胞参与抗寄生虫感染的机制及其意义,为以NK细胞为靶点的寄生虫防治提供理论依据。     

白细胞介素37在感染性疾病中的作用

白细胞介素37(IL-37)是IL-1家族的细胞因子,可在多种细胞中表达。IL-37可通过负反馈免疫调节机制调节先天性和适应性免疫系统,具有抑制炎症反应的作用。在抗感染免疫应答中,IL-37可通过抑制单核细胞、树突状细胞的功能抑制细菌、病毒和真菌等病原生物感染引起的炎症反应,减轻病原体或免疫应答对机体的损伤,从而在感染性休克的防治中发挥作用,另一方面,IL-37也可通过抑制单核巨噬细胞和中性粒细胞等免疫细胞的功能,影响机体抗感染免疫应答,导致病原微生物不能被及时清除,引起持续感染或严重感染,本文就IL-37在感染性疾病中的作用进行综述。     

记忆性NK细胞生物学特性的研究进展

免疫记忆是适应性免疫应答获得的防止再感染的重要特征。固有免疫细胞如NK细胞在感染或细胞因子诱导下亦可获得免疫记忆。与传统NK细胞相比,记忆性NK细胞具有抗原特异性,细胞毒性功能增强和长期存活等特性。深入探讨细胞、分子和微生物对NK细胞记忆的影响,对提升疫苗效果和抗肿瘤作用具有重要意义。为此,本文对记忆性NK细胞的表型、免疫记忆特征和生物学功能及在临床中的应用作以综述。     

白细胞介素对NK细胞的调控作用及其分子机制

自然杀伤(natural killer,NK)细胞是一种大颗粒淋巴细胞,能够介导非特异性免疫应答,在机体抗肿瘤、抗感染等过程中发挥重要作用。白细胞介素通过影响NK细胞的分化、成熟、增殖和细胞毒作用参与对其免疫功能的调控。本文综述了白细胞介素对NK细胞功能的调控作用及其可能的分子机制。     

记忆性NK细胞的研究进展

自然杀伤细胞(Natural Killer cells,NK cells)作为固有免疫系统的重要组成部分,可以在无预先活化的情况下对病原体的入侵作出快速广泛的应答,杀伤靶细胞并释放细胞因子,尤其是IFN-γ.然而最近的研究表明,NK细胞跨越了传统意义上固有免疫和适应性免疫的界限,不仅发挥固有免疫的作用,而且具备适应性免疫的所有特点甚至包括记忆性,通过识别活化性受体或细胞因子可以诱导记忆性NK细胞的形成.     

CD226 对 CD4+T 细胞调节作用的研究进展

CD226 为表达于NK 细胞、T 细胞、单核细胞等多种免疫细胞膜上的一种玉型跨膜糖蛋白,与配体CD112 或CD155 结合后,通过介导多种免疫细胞的分化、增殖和功能调节来参与机体多项生理和病理活动。本文围绕CD226 对于CD4+ T 细胞的免疫调控作用和参与疾病进程的研究进展展开综述,重点阐明CD226 参与初始CD4+ T 细胞增殖分化、Th1/ Th2/Th17 细胞极化过程和对调节性T 细胞的调控作用。     

5-羟色胺与免疫系统的关系及其在免疫相关疾病中的作用

5-羟色胺(5-HT)是一种由色氨酸衍生而来的自体活性物质,主要作为神经递质影响神经系统的功能。近年来研究发现,5-HT通过结合表达在免疫细胞上的受体,调节免疫细胞功能,在机体神经免疫调节网络中发挥重要作用。本文主要综述了5-HT在免疫细胞中的合成和储存,对固有免疫应答、适应性免疫应答的影响以及与免疫相关疾病的关系。     

胸腺基质淋巴细胞生成素对免疫细胞的调控作用及其研究进展

胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin, TSLP), 作为一种多效性的细胞生长因子, 不仅参与人体皮肤纤维化、表皮增生以及血管生成等过程, 同时还对免疫相关疾病(如呼吸系统疾病、过敏性疾病等)中多种免疫细胞具有调控作用, 是免疫细胞的关键调控因子。TSLP主要通过TSLP受体介导的JAK/STAT、NF-κB等信号通路, 参与调控多种固有免疫细胞(如树突状细胞、肥大细胞、巨噬细胞、嗜酸性粒细胞、嗜碱性粒细胞、自然杀伤性T细胞、固有淋巴细胞)以及适应性免疫应答细胞(T和B淋巴细胞等)的分化、增殖过程与功能。现就近年来TSLP对多种免疫细胞增殖、分化及功能的调控研究进展作一综述。     

Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function

Metabolic flux can dictate cell fate, including immune cell effector and regulatory function. The metabolic regulation of cell function is well characterized with respect to effector, memory, and regulatory T cells. This knowledge may allow for manipulation of T cell metabolic pathways that set the stage for more effective T cell therapy. Natural Killer (NK) and T-lymphocytes have complementary roles in the defense against pathogens. However, studies of NK cell metabolism are only beginning to emerge and there is comparatively little knowledge on the metabolic regulation of NK-cell activation and effector function. Given their common lymphoid lineage, effector functions and cellular memory potential our current knowledge on T cell metabolism could inform investigation of metabolic reprogramming in NK cells. In this review, we compare the current knowledge of metabolic regulation in T cell and NK cell development, activation, effector and memory function. Commonalties in glucose transport, hypoxia-inducible factors and mTOR highlight metabolic control points in both cells types. Contrasting the glycolytic and oxidative nodes of metabolic regulation in T cells versus NK cells may provide insight into the contribution of specific immune responses to disease and promote the development of immunotherapeutic approaches targeting both innate and adaptive immune responses.     

Activation of natural killer cells: underlying molecular mechanisms revealed

Natural killer (NK) cells, the third major lymphocyte population, are important effector cells against certain infections and tumours. They have also been implicated as a link between innate and adaptive immune responses. In recent years, much attention has been paid to the NK cell inhibitory receptors and their interaction with major histocompatibility complex class I molecules on target cells. This review summarizes recent findings on regulation of NK cell activity with an emphasis on NK cell stimulatory receptors. A particular emphasis is devoted to the receptor NKG2D that is expressed on all NK cells.     

Control of NK cell functions by CD4+CD25+ regulatory T cells

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance. As a result of suppressive effects on CD4+ and CD8+ effector T cells, Treg control the adaptive immune system and prevent autoimmunity. In addition, they inhibit B lymphocytes, dendritic cells, and monocytes/macrophages. It is interesting that several recent papers show that CD4+CD25+ Treg are also able to inhibit NK cells. Thus, Treg exert their control on immune responses from the onset (triggering of innate immune cells) to the effector phase of adaptive immunity (B and T cell-mediated responses). That Treg inhibit NK cells suggests that their uncontrolled activation might break self-tolerance and induce "innate" autoimmune pathology. Conversely, Treg-mediated suppression of NK cell functions might have negative effects, as these cells are important in defense against infections and cancer. It is conceivable that Treg might dampen efficient activation of NK cells in these diseases.     

Regulation of adaptive immunity by natural killer cells

Natural killer (NK) cells are well recognized as cytolytic effector cells of the innate immune system. In the past several years, the structure and function of NK cell receptors for the major histocompatibility complex (MHC) class I molecules and other ligands have been the subject of extensive studies. These studies have focused largely on the mechanisms of target cell recognition for lysis. Another aspect of NK cell function that seems to be underappreciated is their role in immune regulation. Since NK cells produce a number of immunologically relevant cytokines, it has been suggested that these cells may modulate the development of the adaptive immune response. But, is it the only mechanism by which NK cells interact with cells involved in the induction of antigen-specific responses? This article reviews some older and more recent studies and attempts to place NK cells in the context of potent immune regulators of T cell responses.     

Early liaisons between cells of the innate immune system in inflamed peripheral tissues

The crosstalk between natural killer (NK) cells and myeloid dendritic cells (DCs) results in NK-cell activation and DC maturation. Activated NK cells acquire the ability to kill DCs that have failed to undergo complete maturation ('DC editing'). Recent studies have revealed that this crosstalk can be promoted by pathogen-derived products that activate different innate immune cell types directly and simultaneously through their Toll-like receptors (TLRs). These cells include NK cells and DCs, as well as plasmacytoid DCs (PDCs) and mast cells. This crosstalk can have a great impact on the quality and strength of the subsequent adaptive immune response. Thus, NK cells have an important role in the defense against pathogens, acting as regulatory cells as well as effector cells.     

Tricking the balance: NK cells in anti-cancer immunity

Natural Killer (NK) cells are classically considered innate immune effector cells involved in the first line of defense against infected and malignant cells. More recently, NK cells have emerged to acquire properties of adaptive immunity in response to certain viral infections such as expansion of specific NK cell subsets and long-lasting virus-specific responses to secondary challenges. NK cells distinguish healthy cells from abnormal cells by measuring the net input of activating and inhibitory signals perceived from target cells through NK cell surface receptors. Acquisition of activating ligands in combination with reduced expression of MHC class I molecules on virus-infected and cancer cells activates NK cell cytotoxicity and release of immunostimulatory cytokines like IFN-γ. In the cancer microenvironment however, NK cells become functionally impaired by inhibitory factors produced by immunosuppressive immune cells and cancer cells. Here we review recent progress on the role of NK cells in cancer immunity. We describe regulatory factors of the tumor microenvironment on NK cell function which determine cancer cell destruction or escape from immune recognition. Finally, recent strategies that focus on exploiting NK cell anti-cancer responses for immunotherapeutic approaches are outlined.     

The Natural Killer Cell – Friend or Foe in Autoimmune Disease?

Autoimmune diseases are chronic conditions resulting from a loss of immunological tolerance to self-antigens. Recent observations have supported an ever-broader role for innate immune responses in directing and regulating adaptive immunity, including responses to self. This review summarizes recent findings supporting important functions of natural killer (NK) cells in regulating autoimmunity. A close survey of the current literature reveals multiple steps where NK cells can regulate inflammation and intervene in loss of self-tolerance. Importantly, the findings also caution against inferring a similar role for NK cells in all autoimmune phenomena or during separate stages of the same disease. Indeed, NK cells may have different influences during the priming and the effector phases of disease. Hence, an increased understanding of the involvement of NK cells in inflammation and infection should provide new insights into the pathogenesis of autoimmune disease.     

Innate immunity and chronic immune activation in HCV/HIV-1 co-infection

Innate immune responses are critical in the defense against viral infections. NK cells, myeloid and plasmacytoid dendritic cells, and invariant CD1d-restricted NKT cells mediate both effector and regulatory functions in this early immune response. In chronic uncontrolled viral infections such as HCV and HIV-1, these essential immune functions are compromised and can become a double edged sword contributing to the immunopathogenesis of viral disease. In particular, recent findings indicate that innate immune responses play a central role in the chronic immune activation which is a primary driver of HIV-1 disease progression. HCV/HIV-1 co-infection is affecting millions of people and is associated with faster viral disease progression. Here, we review the role of innate immunity and chronic immune activation in HCV and HIV-1 infection, and discuss how mechanisms of innate immunity may influence protection as well as immunopathogenesis in the HCV/HIV-1 co-infected human host.     

自然杀伤细胞活化性受体的研究进展

自然杀伤细胞（NK）是机体固有免疫系统的重要效应细胞,其不仅能杀死病毒感染细胞和肿瘤细胞,还参与调节固有免疫应答和适应性免疫应答.NK细胞对靶细胞的杀伤效应取决于NK细胞抑制性受体和活化性受体与其配体相互作用的整合,而NK细胞不杀伤正常组织是因为抑制性受体对HLA-Ⅰ类分子的优势识别.NK细胞抑制性受体研究比较成熟,近几年NK细胞活化性受体研究进展很快.     

Line of attack: NK cell specificity and integration of signals

Natural killer (NK) cells possess potent cytolytic activity and secrete immune modulating cytokines. The large repertoire of NK cell receptors provides versatility for the identification of infected and transformed cells and for their elimination by NK cells. NK cell responses also stimulate and regulate the adaptive arm of the immune system. We review current knowledge about the molecular specificity of NK cell receptors and about the regulation of NK cell effector functions upon encounter with target cells. Mechanisms of recognition, interplay among receptors, signal integration, and the dynamic fine-tuning of NK cell responses are discussed. New insights into the molecular checkpoints for NK cell effector function are highlighted, and underlying reasons for the complexity in NK cell recognition and signaling are proposed.