Arginase and its mechanisms in Leishmania persistence

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.     

黑素细胞及相关细胞群参与白癜风发病的研究进展

【摘要】 白癜风发病机制复杂，黑素细胞缺失是核心。目前认为除黑素细胞自身缺陷外，表皮和真皮细胞群的功能异常及其与黑素细胞的交互作用对白癜风的发病同样重要，充分而准确地了解不同病期白癜风皮肤全层细胞、组织的病理生理状态，对认识和治疗白癜风有重要作用。本文旨在综述黑素细胞及相关细胞群在白癜风发病中作用的研究进展。     

诱导性协同共刺激分子及程序性死亡受体1在大疱性类天疱疮皮损中的表达及意义

【摘要】 目的 通过检测滤泡辅助性T细胞（Tfh）相关分子诱导性共刺激分子（ICOS）及程序性死亡受体1（PD?1）在大疱性类天疱疮（BP）患者皮损中的表达，探讨Tfh在BP发病机制中的作用。方法 收集大连市皮肤病医院2014—2017年间确诊的BP患者石蜡组织标本21份，其中女7例，男14例，平均年龄72.57岁。应用免疫组化SP法检测BP皮损中ICOS与PD?1的表达，以10例正常皮肤组织作为对照组。结果 ICOS、PD?1在BP皮损中均主要表达于表皮基底层、棘细胞层、颗粒层、角质层，以棘细胞层表达最为显著，细胞质、细胞核均见表达，偶见细胞膜表达，真皮层炎症细胞中亦有表达；正常皮肤组织中ICOS、PD?1表达少见。BP组ICOS表达率为85.71%（18/21），PD?1表达率为47.62%（10/21），均高于正常对照组（均为0），差异有统计学意义（P值分别＜0.001、＜0.05）。结论 Tfh细胞相关分子ICOS、PD?1在BP发病机制中可能发挥重要作用。     

The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update

So far, innate immune mechanisms have been recognized as the main responsible for the evolution of both alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). However, increasing evidence points toward the possible role of adaptive immune responses, as an additional factor in promoting hepatic inflammation in steatohepatitis. In this article, we discuss recent data involving circulating antibodies and lymphocyte-mediated responses in sustaining the progression of ASH and NASH to fibrosis, as well as the possible mechanisms implicated in favoring the onset of adaptive immunity in the setting of steatohepatitis.     

“消银解毒饮”对银屑病血热证外周血淋巴细胞调控作用研究

目的：观察正常人及银屑病患者应用消银解毒饮治疗前后外周血T淋巴细胞及共刺激因子表达的变化，探讨“消银解毒饮”对银屑病血热证外周血淋巴细胞调控作用。方法：治疗组给予连续8周消银解毒饮治疗，用流式细胞术检测，与对照组相互比较外周血T细胞亚群及共同刺激分子CD28、CD80、CD86的表达情况。结果：治疗组治疗后皮损评分降低；治疗前后与正常人相比CD3+、CD4+细胞及CD4+/CD8+降低，CD8+细胞升高；CD28疗前高于、疗后低于正常组；CD86治疗前后均明显高于正常组；CD80正常组与治疗前均无明显统计学意义，治疗后有下降的趋势。治疗组治疗前、后外周血T细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+和共刺激因子CD28、CD80、CD86均无明显的统计学意义。结论：消银解毒饮临床疗效肯定；银屑病患者外周血T细胞亚群及共刺激因子的表达存在异常；患者临床症状的好转与外周血T细胞亚群及共刺激因子表达的改变是否平行相关尚不确定。     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

Notch信号通路调控Treg/Th17细胞机制的研究进展

摘要： Notch家族是多细胞生物发育过程中一类高度保守的、 十分重要的跨膜信号蛋白, 通过与相邻细胞之间的相互作用, 在细胞增殖、 分化、 凋亡中发挥着关键作用。调节性T细胞 （Treg） 及辅助性T细胞17 （Th17） 是目前发现的一类新型CD4+ T细胞亚群, 在生理状态下, 两者可通过分泌多种细胞因子来调节机体免疫的平衡。近年来, 越来越多的研究发现Notch信号通路通过调控Treg、 Th17细胞参与机体多种疾病的发生。本文就Notch信号通路在血液系统疾病、 自身免疫系统疾病等疾病中对Treg/Th17细胞调控机制的研究进展作一简要综述。     

CD8阳性T细胞亚群在肺癌外周血的检测及分析

目的 检测肺癌患者外周血清中CD8⁺T细胞亚群CD28⁺及CD57⁺的表达程度,探讨其临床意义。 方法 合肥市第二人民医院经细胞学或病理学诊断为肺癌的初次治疗患者30例, TNM分期(UICC,第7版)Ⅲ期12例,Ⅳ期18例。病理类型腺癌15例,鳞癌8例,小细胞肺癌7例。流式细胞仪分别检测肺癌患者组治疗前后及健康对照组人群的血清中CD8⁺T细胞CD28⁺和CD57⁺的表达水平,分析该表达水平变化及与肺癌临床分期和病理学类型之间的关系。 结果 肺癌患者治疗前血清中CD28⁺T细胞亚群比例为(12.34±3.72)%,CD57⁺ T细胞亚群比例为(19.53±5.26)%。而健康对照组血清中CD28⁺T细胞亚群比例为(23.53±4.15)%,CD57⁺ T细胞亚群比例为(11.37±2.73)%,差异有统计学意义(P<0.05),该类指标与肿瘤病理类型无关,而随着不同临床分期增加,CD8⁺CD57⁺T细胞未见差异,而CD8⁺CD28⁺T细胞表达差异有统计学意义(P<0.05)。经两周期化疗后,缓解组(完全缓解+部分缓解)患者血清中CD28⁺、CD57⁺T细胞亚群比与健康对照组患者相比,差异无统计学意义(P>0.05),而未缓解组(稳定+进展)患者的CD28⁺、CD57⁺T细胞亚群比例分别为(10.62±2.74)%、(20.45±4.36)%.与健康对照组差异有统计学意义(P<0.05)。 结论 肺癌患者血清中CD8⁺CD28⁺T细胞表达较正常人群明显减低,而CD8⁺CD57⁺T细胞表达较正常人群明显升高,联合该两种T细胞亚群检测不仅可以了解肺癌患者免疫状况,同时可以评估肺癌患者预后,有一定临床应用价值。     

Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions

Introduction: Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response.

Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease.

Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.     

茶多酚对复发性阿弗它溃疡大鼠模型外周血T淋巴细胞亚群的影响

目的：探讨细胞免疫与复发性阿弗它溃疡（recurrent aphthous ulcer，RAU）发病机制的关系及茶多酚（tea polyphenols，TP）对RAU的免疫调节作用。方法：用免疫方法建立SD大鼠RAU动物模型，将RAU大鼠随机分成阴性对照组、溃疡糊剂组和3个TP治疗组。用流式细胞仪检测成模前后及用药前后各组大鼠外周血T淋巴细胞亚群CD4^＋、CD8^＋细胞数量及比值。结果：实验大鼠溃疡模型成模后外周血CD4^＋及CD4^＋／CD8^＋较成模前显著降低（P〈0．01），CD8^＋改变无统计学意义（P〉0．05）。茶多酚各治疗组外周血CD4^＋、CD4^＋／CD8^＋回升，与阴性对照组有显著性差异（P〈0．05），茶多酚各治疗组间比较没有显著性差异（P〉0．05）。结论：RAU的发生与细胞免疫功能抑制有关，TP对大鼠RAU具有免疫调节作用，其免疫调节作用与给药方式无关。