New insights into roles of basophils in initiating T helper type 2 immunity

Allergic diseases, mainly mediated by T helper type 2(Th2) immunity, have become a worldwide public health problem. Traditional Chinese medicine(TCM) has long been used in treating and preventing allergic symptoms. As the new target of anti-allergy TCM, basophils, after approximately 140 years since their discovery, are just now gaining respect as important contributors in the pathogenesis underlying allergic inflammation and disease. In addition to their role as effector cells, basophils can release early IL-4, migrate from circulatory system into draining lymph nodes, present antigen to naive CD4~+T cells,and promote the differentiation of Th2 cells. Herein, we briefly summarized the recent research advances of the essential contributions of basophils in the initiation of Th2 immune responses.     

Traditional Korean medicine (SCRT) modulate Th1/Th2 specific cytokine production in mice CD4+ T cell

Traditional Korea medicine, So-Cheong-Ryong-Tang (SCRT) also called as Xiao-qing-long-tang or Sho-seiru-to, contains eight species of medicinal plants and has been used for treating allergic diseases, such as allergic rhinitis and asthma, for hundreds of years in Asian countries. CD4+ T cells were highly purified by using magnetic bead from splenocytes of BALB/c mice. SCRT treatment slightly decreased the expression of cell surface protein CD69 on CD4+ T cell in the flow cytometry analysis. In RT-PCR analysis, SCRT increases the expression of IL-2 and IL2R-alpha mRNA, and decreases the expression of IL-4 mRNA, which is an important cytokine of Th2 cell development. On the other hand, SCRT treatment increases IFN-gamma expression, which is one of the key cytokines for Th1 cell development. Present study implies that SCRT can correct Th2 dominant condition directly affecting to the CD4+ T cell without significantly depressing general T cell activities. These results also suggest that the effect on CD4+ T cell may be the one of key pharmacological effect point for treating IgE medicated allergic asthma by SCRT.     

中医药干预溃疡性结肠炎Th17/Treg平衡的研究进展

溃疡性结肠炎(UC)是一种常见的慢性非特异性的肠道炎症,其病程长且难以治愈,发病率逐年上升。辅助性T细胞17(Th17)是免疫促进细胞之一,而调节性T细胞(Treg)是一种免疫抑制细胞,Th17和Treg细胞共同维持着机体免疫微环境的平衡。在UC进展期间,引起炎症的Th17群体通常增加,而抑制Th17活性的Treg减少。其中,Th17介导免疫应答反应,Treg介导免疫抑制,两者协调平衡在溃疡性结肠炎的炎症和免疫过程中起关键作用。UC的西医治疗虽具有一定的效果,然而,副作用的频率和严重程度,不方便的剂量调节,以及部分价格过高限制了他们的临床应用。中药作为我国的传统医药,具有多靶点、多环节、多途径的治疗特点,在抗溃疡性结肠炎方面具有独特优势和广阔前景。近年来,中医药领域以Th17/Treg平衡为切入点,开展了大量中医药干预UC中Th17/Treg平衡的临床和实验研究,并取得了一定的成果,临床和实验证据明确表明干预Th17/Treg是中医药治疗溃疡性结肠炎的重要作用机制。本文主要对前人关于中药单体、组分或有效成分、中药复方对UC中Th17/Treg平衡的干预作用研究进行了总结与分析,有利于人们更为准确、全面地认识中医药干预UC中Th17/Treg平衡的作用机制,为临床合理设计抗溃疡性结肠炎治疗方案提供参考。     

基于中医体质理论的脱敏止嚏汤对变应性鼻炎Th1/Th2平衡调控机制探讨

变应性鼻炎（AR）,顽固难愈、复发率高,严重影响患者的生活质量。中医体质学认为AR等过敏性疾病与自身体质密切相关,过敏体质人群机体免疫调适能力低下、对外界致敏原反应增强是导致AR的根本原因。全国名老中医药专家王琦教授从调体入手自拟脱敏止嚏汤,临床观察可有效防治AR。现代免疫学理念认为Th亚群极化后的细胞因子类型决定了机体免疫系统对致敏原的应答状态,鼻腔黏膜Th2极化趋向是AR发生的关键环节,也是干预的重要切入点。前期研究亦发现过敏体质人Th亚群细胞因子调节紊乱。由此提出：Th亚群极化异常是过敏体质的主要分子机制,也是脱敏止嚏汤调体治疗AR的主要作用机理,通过调节Th1/Th2平衡可以从根本上阻断AR的发生发展。     

Suppressive effects of Houttuynia cordata Thunb (Saururaceae) extract on Th2 immune response

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb (Saururaceae), known as 'E-Sung-Cho' in Korea, has been traditionally used for the treatment of herpes simplex, chronic sinusitis, and allergy. AIM OF THE STUDY: To investigate the inhibitory activity of Houttuynia cordata Thunb fractions (HcFs) on the T helper 2 (Th2) immune response, we evaluated the alternation of the release of Th2-type cytokines and chemokines such as interleukin (IL)-4 and IL-5, and thymus and activation-regulated chemokine (TARC/CCL17). MATERIALS AND METHODS: Ethanol fraction was obtained from dried and powdered whole plants of Houttuynia cordata Thunb using ethanol. The residue was diluted with water and was then successively partitioned with n-hexane, EtOAc and BuOH. HcFs include ethanol, n-hexane, EtOAc, BuOH and water fractions. RT-PCR and ELISA were performed to measure mRNA and protein expression of cytokines. RESULTS: HcFs inhibited the expression of IL-4 and IL-5 in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (CaI) in Jurkat T cells and the human mast cell line, HMC-1. IL-4- and tumor necrosis factor-alpha (TNF-alpha)-induced TARC production was blocked by HcFs in skin fibroblast CCD-986sk cells, particularly by the ethanol extract of Hc. Stimulants included in PMA, phytohemagglutinin (PHA) and CaI, increased the mRNA level of CC chemokine receptor 4 (CCR4), a receptor of TARC, in Jurkat T cells, and the ethanol extract of HcF weakly blocked the increased mRNA level. However, the stimulants and ethanol extract had no effect on the CCR4 protein level. The ethanol extract inhibited TARC-induced migration, as well as basal migration of Jurkat T cells. CONCLUSIONS: This study may show the usefulness of HcFs in the ethnopharmacological treatment of Th2-mediated or allergic inflammation, through the down-regulation of the production of Th2 cytokines and TARC, as well as cell migration.     

自拟通窍止鼽汤联合针刺治疗变应性鼻炎发作期临床观察

目的观察自拟通窍止鼽汤联合针刺治疗变应性鼻炎发作期临床疗效及Th9细胞、白细胞介素-9(IL-9)改变。方法选取2018年7月至2020年3月首都医科大学附属北京同仁医院收治的80例变应性鼻炎患者为研究对象,随机分为联合组与对照组各40例。两组均予以西医常规治疗,对照组加用针刺治疗,联合组在对照组治疗基础上增用自拟通窍止鼽汤,两组均治疗2周。比较两组中医证候疗效、主要症状评分、Th9细胞比例及IL-9水平,记录两组治疗期间不良反应。结果联合组中医证候疗效总有效率明显高于对照组(P<0.05)。联合组治疗后7、14 d的鼻塞、鼻痒、喷嚏、流涕症状评分明显低于对照组(P<0.05)。两组治疗后Th9细胞比例及IL-9水平较治疗前明显下降,且联合组明显低于对照组(P<0.05)。两组未见严重不良反应。结论自拟通窍止鼽汤联合针刺治疗发作期变应性鼻炎疗效良好,能明显改善患者临床主要症状,降低Th9细胞比例及IL-9水平。     

加味茵陈蒿汤联合常规治疗对慢性持续期湿热型支气管哮喘患者的临床疗效

目的探讨加味茵陈蒿汤联合常规治疗对慢性持续期湿热型支气管哮喘患者的临床疗效。方法 128例患者随机分为对照组和观察组,每组64例,对照组给予常规治疗(孟鲁司特钠、吸入型β2受体激动剂等),观察组在此基础上加用加味茵陈蒿汤,疗程4周。检测临床疗效、中医证候评分、儿童哮喘控制测试问卷(C-ACT)评分、呼气峰流量(PEF)、辅助性T细胞17(Th17)、调节性T细胞(Treg)、Th17/Treg、白介素-17(IL-17)、转化生长因子-β1(TGF-β1)、不良反应发生率变化。结果观察组总有效率高于对照组(P<0.05)。治疗后,2组中医证候评分、Th17、Th17/Treg、IL-17降低(P<0.05),C-ACT评分、PEF、Treg、TGF-β1升高(P<0.05),以观察组更明显(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论加味茵陈蒿汤联合常规治疗可有效调控慢性持续期湿热型支气管哮喘患者外周血Th17/Treg细胞平衡,缓解临床症状,改善肺功能,耐受性较好。     

Xiaoqinglong decoction reduces dendritic cell differentiation and regulates the Th1/Th2 balance in a mouse model of allergic asthma

BackgroundXiaoqinglong decoction (XQLD) is a classic Chinese medicinal formula that is widely used to treat allergic asthma. Recently, the use of XQLD to treat allergic asthma has inspired research to determine its mechanism of action. Because dendritic cells (DCs) and the T helper 1 (Th1)/Th2 cytokine balance play important roles in allergic asthma, the present work aimed to assess how these immune system components are affected by XQLD.MethodsThirty-six female BALB/C mice were randomly divided into three groups: an ovalbumin-based allergic asthma model group, a XQLD treatment group, and a control group. Histology was performed with haematoxylin and eosin staining and immunohistochemical staining. Bronchoalveolar lavage fluid and blood were collected from the animals and used to analyze the composition of inflammatory cells and expression levels of the cytokines interleukin (IL)-5 and IL-13. The thymic stromal lymphopoietin (TSLP) protein expression was assessed by western blot analysis, and the Gata3 and Tbx21 mRNA levels were assessed by polymerase chain reaction.ResultsCompared with the OVA group, the levels of TSLP expression, IL-5, IL-13, and immunoglobulin E in the XQLD group were lower (all P < .01). The level of IL-4-expressing cells (Th2 cells) was lower (P = .0013), and the percentage of IFN-γ-expressing cells (Th1 cells) was higher in the XQLD group compared with those in the OVA group (P = .0065). In addition, XQLD increased the expression of Tbx21 mRNA and decreased the expression of Gata3 mRNA in the lungs compared with the OVA group (both P < .01).ConclusionThese findings suggest that XQLD may ameliorate the course of allergic asthma by regulating the Gata3/Tbx21 balance and inhibiting TSLP expression, changes which are indicative of an altered Th1/Th2 balance. Thus, the clinical effectiveness of XQLD in treating allergic asthma may be due to its regulation of Th1/Th2 balance.     

Immunomodulatory activity of isoflavones isolated from Iris germanica (Iridaceae) on T‐lymphocytes and cytokines

The immunomodulatory activities of two isoflavones, 5,7‐dihydroxy‐6,4′‐dimethoxyisoflavone (irisolidone) (1) and 5,4′‐dihydroxy‐6,7‐methylenedioxyisoflavone (irilone) (2) isolated from Iris germanica (Iridaceae) is reported. Their influence on production of T‐lymphocytes (CD4+ and CD8+ cells) and T‐cell cytokines, namely Th1: IL‐2, IFN‐γ and Th2: IL‐4 and IL‐5 in a dose‐dependent manner was studied by flow cytometric method in Balb/c mice. Oral administration of drugs at doses of 0.1–0.8 mg/kg per oral dose showed 1 to possess stimulatory activity on T‐cells and Th1 cytokine production, while as 2 acted as an immunosuppressant for both cells and cytokines. The methylated products of 1 and 2 showed a similar trend to that of their parent compounds but their activity was drastically decreased revealing the importance of free phenolic groups for their immunomodulating activities. Copyright © 2008 John Wiley & Sons, Ltd.     

再生障碍性贫血选用免疫抑制剂或雄激素治疗预测指标的初步研究

目的 研究和评价以外周血T细胞亚群、Th1/Th2、T-bet和GATA-3基因表达及中西医诊断标准为主建立的多变量指标,作为再生障碍性贫血（AA）患者选用免疫抑制剂或雄激素的预测指标。方法 采用流式细胞术检测85例AA患者治疗前后外周血T细胞亚群, 同时运用实时定量PCR技术检测T-bet和GATA-3基因表达, 并以免疫抑制剂和雄激素有效病例做Logistic回归方程及ROC曲线分析。 结果 （1）按SPSS的ROC曲线模型, 设定假阳性率为0.10, 取P值为0.832, 若P值≥0.832时, 判定患者为免疫紊乱状态, 应加用免疫抑制疗法（IST）治疗;若P值< 0.832时, 判定患者为骨髓衰竭状态, 应加用雄激素治疗。（2）提出AA在疾病发生发展过程中可大致分为以异常免疫为主和以骨髓衰竭为主两个阶段, 以异常免疫为主应加用IST治疗;以骨髓衰竭为主应加用雄激素治疗。 结论 上述预测方法可判断AA患者处于以异常免疫为主或以骨髓衰竭为主状态, 指导免疫抑制剂或雄激素的临床应用。     

中药联合窄谱中波紫外线对白癜风患者治疗效果及对其免疫功能的影响

目的:探讨中药联合窄谱中波紫外线(NB-UVB)对白癜风的治疗效果及对患者免疫功能的影响。方法:选取2015年4月至2016年10月海南省皮肤病医院收治的白癜风患者98例,随机分为对照组和观察组,每组49例。对照组均进行NB-UVB治疗,观察组在此基础上结合白驳汤治疗,2组均连续治疗3个月。统计2组临床疗效;比较2组治疗前后白癜风病变面积改善情况;检测并比较治疗前后2组T淋巴细胞亚群比例及粒细胞-巨噬细胞集落刺激因子(GM-CSF)及白细胞介素-4(IL-4)、γ-干扰素(IFN-γ)表达和Th1/Th2。结果:治疗后观察组总有效率为81.63%,明显高于对照组的61.22%(P0.05)。治疗后2组白癜风病变面积均减小,且观察组明显小于对照组(P0.05)。治疗后2组CD4+、CD4～+ CD25～+Treg细胞比例及CD4+/CD8～+比值升高,CD8～+细胞比例及GM-CSF水平降低(P0.05),且2组间差异有统计学意义(P0.05)。治疗后2组血清IL-4水平升高,IFN-γ水平及Th1/Th2比值降低(P0.05)。结论:中药联合NB-UVB治疗白癜风疗效显著,可提高患者免疫功能,调节相关细胞因子的表达,延缓了疾病的进展,安全有效。     

Morin promotes the production of Th2 cytokine by modulating bone marrow-derived dendritic cells

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-alpha in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-gamma in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.     

定喘汤联合西医常规治疗对过敏性支气管哮喘患者外周血单个核细胞Th1/Th2及黏膜免疫功能的影响

目的观察定喘汤联合西医常规治疗对过敏性支气管哮喘患者外周血单个核细胞Th1/Th2及黏膜免疫功能的影响。方法将80例过敏性支气管哮喘患者按随机数字表法分为2组,对照组40例予西医常规治疗,治疗组40例在对照组治疗基础上加用定喘汤治疗。2组均治疗4周后统计临床疗效,并观察2组治疗前后喘息、咳嗽、咯痰及哮鸣音症状积分,第1 s用力呼气容积(FEV_1)、FEV_1/用力肺活量(FVC)、第1 s用力呼气容积占预计值百分比(FEV_1%),外周血单个核细胞辅助性T细胞1百分率(Th1)、外周血单个核细胞辅助性T细胞2百分率(Th2)、Th1/Th2,气道基质金属蛋白酶-9(MMP-9)评分、嗜酸性粒细胞计数,以及不良反应发生情况。结果 2组治疗后喘息、咳嗽、咯痰及哮鸣音中医症状积分均改善(P0.05),且治疗组改善优于对照组(P0.05)。2组治疗后FEV_1、FEV_1/FVC、FEV_1%、Th1百分率、Th2百分率、Th1/Th2、气道MMP-9评分及嗜酸性粒细胞计数均改善(P0.05),且治疗组改善优于对照组(P0.05)。治疗组总有效率90.00%,对照组总有效率60.00%,2组比较差异有统计学意义(P0.05),治疗组疗效优于对照组。2组间不良反应发生率比较差异无统计学意义(P0.05)。结论定喘汤联合西医常规治疗过敏性支气管哮喘疗效确切,并能改善临床症状、肺功能、外周血单个核细胞TH1/TH2及黏膜免疫功能。     

Suppression of T lymphocyte activity by lupeol isolated from Crataeva religiosa

Lupeol has been shown to possess antiarthritic activity through possible suppression of the immune system. As seen in the following studies, it was found to suppress various immune factors such as the phagocytic (cell-killing) activity of macrophages, T-lymphocyte activity that included CD4+T cell mediated cytokine generation. Assessment of T cells and their intracellular content of cytokines was carried out by flow cytometric analysis in Balb/c mice. Oral administration of lupeol at doses of 12.5-200 mg/kg p.o. inhibited CD4+ T and CD8+ T cell counts and cytokines IL-2, IFN-gamma (Th1) and IL-4 (Th2). Cytometric bead array (CBA) technology was applied to carry out simultaneous measurement of multiple serum cytokines. The oral LD(0) in mice was more than 2 g/kg body weight.     

Cytopiloyne, a novel polyacetylenic glucoside from Bidens pilosa, functions as a T helper cell modulator

An extract of Bidens pilosa, an anti-diabetic Asteraceae plant, has recently been reported to modulate T cell differentiation and prevent the development of non-obese diabetes (NOD) in NOD mice. In this paper, a novel bioactive polyacetylenic glucoside, cytopiloyne (1), was identified from the Bidens pilosa extract using ex vivo T cell differentiation assays based on a bioactivity-guided fractionation and isolation procedure. Its structure was elucidated as 2β-d-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne by various spectroscopic methods. Functional studies showed that cytopiloyne was able to inhibit the differentiation of naïve T helper (Th0) cells into type I T helper (Th1) cells but to promote the differentiation of Th0 cells into type II T helper (Th2) cell. Accordingly, cytopiloyne also suppressed IFN-γ expression and promoted IL-4 expression in mouse splenocytes ex vivo. These results suggest that cytopiloyne functions as a T cell modulator that may directly contribute to the ethnopharmacological effect of Bidens pilosa extract on preventing diabetes. Moreover, cytopiloyne can serve as an index compound for quality control of lot-to-lot extract preparations of Bidens pilosa.     

扶正祛邪颗粒对呼吸道病毒感染人群免疫细胞及因子的影响

目的观察扶正祛邪颗粒对呼吸道病毒感染人群免疫细胞及细胞因子的影响。方法59例患者随机分为3组,即治疗组(19例,用常规西药加中药治疗)、西药组(19例,单用常规西药治疗)和中药组(21例,单用中药治疗),分别于治疗前、治疗1周和2周测定T淋巴细胞亚群、白细胞介素(IL-2、4、6、10)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)及Th1／Th2比值的变化。结果3组患者治疗前TNF-α、IL-2、IL-6、IL—10和IFN-γ水平均比健康人明显升高(P<0．05),治疗1周时血清TNF-α、IL-6、IL-10水平比治疗前明显降低(P<0．05);西药组血清IL-2和IFN-γ于第2周时已降至正常,治疗组及中药组至第2周时血清IL-2和IFN-γ浓度仍保持较高水平(P<0．05)。血清IL-4水平3组治疗前后比较差异无显著性。治疗第2周时治疗组和中药组Th1／Th2比值比西药组和治疗前升高(P<0．05);3组T淋巴细胞亚群(CD3^+、CD4^+、CD8^+)和分类(B和NK)细胞百分比治疗前后比较差异无显著性。结论扶正祛邪颗粒在一定程度上能正面调节上呼吸道病毒感染人群的免疫功能。     

Sceptridium ternatum extract exerts antiasthmatic effects by regulating Th1/Th2 balance and the expression levels of leukotriene receptors in a mouse asthma model

Aim of the study

Sceptridium ternatum Lyon (ST), a common Chinese herb, has been used in treatment of allergic asthma and whooping cough. In the present study, we investigated the Th1/Th2 ratio of peripheral blood and mRNA levels of leukotriene receptors after the treatment of ST in allergic asthma mouse model.

Materials and methods

Mouse asthma model was developed by ovalbumin (OVA) sensitization followed by the inhalation of aerosol allergen. Montelukast (10 mg/kg), as a positive control drug, and ST were administrated six days before the OVA sensitization for ten days. Airway responsiveness was evaluated by the Medlab 12.0 biological signal processing system. The ratio of Th1/Th2 cells was determined by flow cytometry. The expression level of Cyslt1 was measured by PCR. Pathological changes of lung tissues were examined by H&E staining.

Results

ST significantly reduced the airway responsiveness, elevated the ratio of Th1/Th2, and decreased Cyslt1 mRNA level in a dose-dependent manner. High-dose ST distinctly prevented the pathological changes of lung tissues.

Conclusion

High-dose ST had the same efficacy as Montelukast in a mouse asthma model, and ST could be a potential anti-asthmatic agent.