microRNA-155的免疫调控作用

miR-155是一种具有免疫调控功能的微小RNA,它能够在转录后降解靶信使RNA或者抑制靶基因的翻译。最近的研究发现它对树突状细胞、巨噬细胞、B细胞、T细胞及调节性T细胞等免疫细胞的分化发育和功能都具有重要的调控作用,某些病毒的miRNA与miR-155具有同源性,在免疫调控中也可能发挥相同作用。随着miRNA研究的深入,miR-155的更多调控作用将浮出水面,尤其是将为探究免疫相关疾病的病理机制和治疗措施提供新思路。     

microRNA调控树突状细胞分化与成熟的机制

树突状细胞(DC)含有不同的异质性亚群,在获得性免疫的启动、定向激活及调节中发挥重要作用.DC的自身发育分化及功能性成熟受细胞因子及转录因子构成的复杂网络调控.近期研究发现,microRNA (miRNA)通过抑制蛋白翻译或降解mRNA转录本来调控基因表达,调节包括免疫系统在内的多种生物学过程.许多miRNA在B、T淋巴细胞、DC、巨噬细胞及其他类型免疫细胞的发育、分化、存活及功能成熟起到重要作用,部分DC相关的miRNA如miR-155和miR-146a同时参与其他免疫细胞的调节.本文综述了DC亚群的功能,靶向不同DC亚群的免疫后果及细胞表面受体的种类;同时也总结了miRNA在DC由髓系前体细胞发育并分化为特异性亚群过程以及其在DC特异性功能中所发挥的重要作用.     

间充质干细胞对免疫细胞的调节及其在自身免疫性疾病中的应用北大核心CSCD

间充质干细胞(MSC)是干细胞家族的重要成员,来源于发育早期的中胚层和外胚层,具有多向分化潜能、造血支持、免疫调控和自我复制等特征。利用MSC的特殊免疫学特性治疗相关疾病,并取得一定的疗效,但是其具体机制尚不明确且多集中在体外MSC对免疫细胞的影响,而动物模型以及人类疾病的关系很少涉及。鉴于此,本文先从MSC的一般生物学特性入手,进而分析MSC分别与T淋巴细胞、B淋巴细胞和树突状细胞(DC)共培养后对T细胞、B细胞和DC等细胞的免疫调节作用,同时利用MSC对不同细胞的免疫调控作用分析比较其临床应用的具体机制。     

Runx3及其免疫调节作用的研究进展

Runx3作为Runx转录因子家族成员通过对细胞发育、信号转导等生物学作用的调控,参与淋巴细胞、树突状细胞等免疫细胞的分化、增殖和成熟,影响着Th1／Th2的平衡、树突状细胞的迁移和B细胞功能,且对肿瘤细胞具有明显的抑制作用,其作为重要的免疫调节和抑瘤基因正引起人们的广泛关注。     

间充质干细胞对免疫细胞的调节及其在自身免疫性疾病中的应用

间充质干细胞(MSC)是干细胞家族的重要成员,来源于发育早期的中胚层和外胚层,具有多向分化潜能、造血支持、免疫调控和自我复制等特征。利用MSC的特殊免疫学特性治疗相关疾病,并取得一定的疗效,但是其具体机制尚不明确且多集中在体外MSC对免疫细胞的影响,而动物模型以及人类疾病的关系很少涉及。鉴于此,本文先从MSC的一般生物学特性入手,进而分析MSC分别与T淋巴细胞、B淋巴细胞和树突状细胞(DC)共培养后对T细胞、B细胞和DC等细胞的免疫调节作用,同时利用MSC对不同细胞的免疫调控作用分析比较其临床应用的具体机制。     

NK细胞代谢途径及其功能

NK细胞是固有免疫系统的重要成员,在免疫应答中发挥关键作用。NK细胞激活主要依赖于其表面表达的活化性受体和抑制性受体间的动态平衡。然而,在许多慢性疾病模型中,NK细胞受体表达失衡,导致杀伤活性及细胞因子产生能力降低,处于免疫失活状态。近年许多研究表明,胞内代谢对包括NK细胞在内的免疫细胞至关重要,代谢改变能够通过影响细胞发育、增殖和活性等调节免疫细胞效应功能发挥。鉴于NK细胞强大的抗肿瘤和抗病毒功能及其重要的临床应用价值,深入研究其代谢特征及机制具有重要意义。本文主要从NK细胞的代谢方式及其相关调控通路、代谢对NK细胞发育、记忆和功能的调控作用以及基于代谢的NK细胞疗法进行综述,阐述代谢对NK细胞生物合成、体内稳定及效应功能的重要作用,以及不同慢性疾病模型中NK细胞失活的代谢相关因素,为NK细胞治疗的临床应用提供坚实的研究依据。     

B淋巴细胞刺激物单克隆抗体的制备与特性鉴定

B淋巴细胞刺激物(Blymphocyte stimulator，BLyS，也称为BAFF、TALL-1、THANK及zTNF4)是1999年发现的TNF超家族中的新成员，与该超家族中的多数成员一样也表达于淋巴组织中，对免疫系统的发育和调节具有重要作用。BLyS作为B细胞的共刺激物，不仅参与了体液免疫的调控，如果强烈刺激B细胞增殖、分化并分泌大量免疫球蛋白；在T细胞介导的免疫应答中可能也发挥着重要作用。     

小胶质细胞生物学特性及对神经元调控作用

小胶质细胞是常驻脑实质内免疫细胞,在生理状态下是高度动态的,表达多种免疫受体与神经递质受体,严格监控着中枢神经系统(CNS)微环境。近来大量研究揭示这类免疫细胞具有积极地调控神经元作用,其潜在的影响了神经元发生、突触修剪,调节突触可塑性,阻止神经毒性。小胶质细胞功能性变化对CNS的发育、成熟及退化有重要作用。     

记忆性NK细胞的最新研究进展

一般认为NK细胞是一种天然免疫细胞,在抗病毒和抗肿瘤中发挥着重要作用。近年来的研究发现,NK细胞像适应性免疫细胞——T和B细胞一样,具有了免疫记忆的能力。早期研究发现半抗原可以诱导记忆性NK细胞并诱发接触性超敏反应,小鼠巨细胞病毒(m CMV)的感染和细胞因子的体外刺激也可以诱导记忆性NK细胞。而近期的研究发现,小鼠的单纯疱疹病毒(HSV)和流感病毒、人巨细胞病毒(h CMV)、灵长类免疫缺陷病毒(SIV)也可以诱导记忆性NK细胞。本文主要总结上述多种实验体系中有关记忆性NK细胞的最新发现和尚未解决的问题。记忆NK细胞的研究将为NK细胞在治疗感染性疾病和肿瘤中提供新的机遇。     

表观遗传学调控滤泡辅助性T细胞分化的研究进展

滤泡辅助性T细胞(Tfh细胞)定位于淋巴滤泡的辅助性T细胞亚群,主要功能为辅助B细胞参与体液免疫应答,对免疫球蛋白的产生有着重要作用。表观遗传学主要研究在基因的核苷酸序列不发生改变的情况下,基因表达的可遗传性变化,是免疫细胞的分化调控机制之一。研究发现Tfh细胞的分化具有可塑性,本文主要综述了表观遗传学调控在Tfh细胞分化方面的研究进展。     

Spin90 Deficiency Increases CXCL13‐Mediated B Cell Migration

SPIN90 regulates actin dynamics, which is important for cell migration control. CXCL13‐mediated B cell migration is essential for B cell immune responses. In this study, we investigated the role of SPIN90 in CXCL13‐mediated B cell migration using Spin90 gene‐deficient mice. Our chemokinesis analysis and transwell cell migration assay showed that SPIN90 is involved in CXCL13‐mediated B cell migration. Moreover, the level of CXCR5, which is CXCL13 receptor, was increased in SPIN90‐deficient B cells compared with wild‐type B cells. Overall, our data suggest that SPIN90 plays an important role in B cell immune responses through the regulation of CXCL13‐mediated B cell migration.     

High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals

A body of evidence indicates that expression of the programmed cell death 1 (PD-1) receptor by activated T cells plays an important role in the down-regulation of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1) and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are less clear. In the current study, we investigated the roles of B7-H1 in DC-mediated regulation of hapten-activated T cells and the delayed-type contact hypersensitivity response in primed animals. We found that the expression of B7-H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells. Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7-H1/DC) suppressed the proliferation of, and cytokine production by, activated T cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the response of sensitized animals to hapten challenge, and this desensitization was hapten-specific. These data indicate that B7-H1 expressed by DC mediates inhibitory signals for activated T cells and suppresses the elicitation of immune responses. The ability of B7-H1/DC to inhibit the function of preactivated T cells in vivo suggests novel strategies for the treatment of immune response-mediated disorders.     

Homeostasis and T cell regulation

Homeostatic regulation of cell numbers is an important principle in biology. Mechanisms that function to maintain or re-establish homeostasis in the immune system include interactions among antigen-presenting cells, regulatory T cells and cytokines. The vital role that homeostatic regulation plays in maintaining a functionally intact immune system is illustrated by the perturbation of the peripheral T cell repertoire that occurs after lymphopenic incidents, which frequently provoke either exacerbated immune or autoimmune responses. Recent studies show that transient states of lymphopenia occur in viral infections and in the neonatal state and might be involved in the development of autoimmune diseases. On the positive side, lymphopenia-provoked T cell expansion might enhance weak immune responses and thereby aid the rejection of tumours or the elimination of parasites.     

Autoreactivity and the positive selection of B cells

The diversity among B‐cell antigen receptor (BCR) specificities is generated by random rearrangement of gene segments during early B‐cell development. While such stochastic recombination of gene segments is important for diversity, it introduces the risk of producing self‐reactive BCRs which might lead to the development of autoimmune diseases. Therefore, it has been proposed that negative selection of autoreactive BCR specificities during early B‐cell development are required to establish tolerance towards self. In fact, transgenic mouse models have identified a number of “tolerance mechanisms” such as receptor editing, clonal deletion and anergy, all of which prevent the development of autoreactive B cells. Recent data, however, reveal that self‐recognition is crucial for the generation of B cells, and that the precursor‐BCR (pre‐BCR), which is essential for early B‐cell development, basically plays the role of an autoreactive BCR. Moreover, although it has become clear that autoreactive B cells are present in the periphery of healthy individuals, the role of autoantigen in their development, persistence and regulation is unclear. This review outlines the important role of autoreactivity in early B‐cell development and presents potential models for the regulation of the activation of peripheral B cells by different forms of self or foreign antigens.     

SETDB1: A perspective into immune cell function and cancer immunotherapy

Oncogene SET Domain Bifurcated 1 (SETDB1)/ESET, an H3K9 methyltransferase, was originally discovered over two decades ago; however, its function in the immune response was not first reported until 2011. SETDB1 immune functions include B cell maturation, T cell activity regulation, and immune escape in cancer cells. In B lymphocytes, SETDB1 mediates the transition from pro-B to pre-B cells and represses endogenous retroviruses (ERV) to encourage B cell lineage differentiation and maturation. SETDB1 alters T cell function by methylating IL-2 and IL-17 promoters and mediating T cell lineage commitment and development. In addition, SETDB1 plays a critical role in ERV silencing within a variety of immune cells, which can indirectly weaken the immune response. Although SETDB1 is critical for normal immune cell function, overexpression in cancer cells negatively impacts immune cell fights against cancer through decreased tumour immunogenicity. Within cancer cells, SETDB1 overexpression represses production and infiltration of antitumour immune cells, mediates immune escape through TE and ERV silencing, represses the type I interferon pathway, and interferes in immune checkpoint blockade (ICB) outcomes by regulation of PD-L1 expression and IFN signalling. In this review, we further discuss the immunological mechanisms of SETDB1 in normal and cancerous cells and its implications in cancer immunotherapy.     

Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment

It has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity.     

Ets-1在系统性红斑狼疮中的研究进展

系统性红斑狼疮(SCE)是一种典型的系统性自身免疫性疾病,其发病机制尚未明确,其中T、B细胞功能异常起着重要作用.转录因子Ets-1作为SLE的易感基因之一在淋巴细胞分化与细胞因子调节上起重要作用.Ets-1除影响B细胞分化和功能外,对T细胞的生存、增殖、发育和功能起重要作用.虽然Ets-1在SLE发病中的确切机制仍尚未明确,但越来越多的研究表明Ets-1在SLE的发生发展中起着重要作用.     

Negative regulation of lymphocyte development and function by the Cbl family of proteins

Summary: Negative regulation of intracellular signaling delivered by the antigen receptors and coreceptors plays an important role in lymphocyte development and activation. Recent data from our laboratory and others have identified the Cbl family of ubiquitin ligases as important negative regulators in both T-cell and B-cell antigen receptor and coreceptor signaling. We show that c-Cbl and Cbl-b, two members of the Cbl family of proteins, play a redundant role in establishing the major histocompatibility complex-dependent development of thymocytes and in thymic selection. They also control the activation threshold and CD28 costimulatory signaling in peripheral T cells. In B cells, c-Cbl and Cbl-b set the B-cell receptor signaling threshold critical for proper B-cell maturation and anergy induction. Biochemical studies indicate that the immune regulation by Cbl proteins correlate with their ubiquitin ligase function. Inactivation of Cbl-b also renders mice resistant to both transplanted and spontaneous tumors due to an enhanced anti-tumor immunity of CD8⁺ T cells. These findings thus place Cbl proteins at the center of a complex immune network regulation and suggest that modulation of this signaling pathway may be beneficiary to the treatment of autoimmunity and cancer.