AIM: To explore the probable pathway by which curcumin(Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells(DCs).METHODS: Experimental colitis was induced...AIM: To explore the probable pathway by which curcumin(Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells(DCs).METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine(Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4+CD25+Foxp3+ T cells(Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules(CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur.CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease.展开更多
CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulator...CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity.展开更多
Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and ...Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line （EL-4 cells） was used. The expressions of CD4, CD25, Nrpl, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-131, IL-10, PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation, the expression of Nrpl increased significantly in 4.0 Gy group, compared with sham-irradiation group （P〈0.05） in the spleen and thymus, respectively, when ICR mice received whole-body irradiation （WBI）. Meanwhile the synthesis of Interleukin 10 （IL-20） and transforming growth factor-β1 （TGF-β1） increased significantly after high dose irradiation （HDR） （〉 or = 1.0 Gy）. In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4＋CD25＋Nrpl＋Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4＋CD25＋Nrpl＋Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.展开更多
目的研究B、T淋巴细胞衰减因子(B and T lymphocyte attenuator,BTLA)及其配体疱疹病毒进入中介体(herpesvirus entry mediator,HVEM)在肺结核患者CD4^(+)CD25^(+)CD127^(low)调节性T细胞(CD4^(+)CD25^(+)CD127^(low)Treg)中的表达及其...目的研究B、T淋巴细胞衰减因子(B and T lymphocyte attenuator,BTLA)及其配体疱疹病毒进入中介体(herpesvirus entry mediator,HVEM)在肺结核患者CD4^(+)CD25^(+)CD127^(low)调节性T细胞(CD4^(+)CD25^(+)CD127^(low)Treg)中的表达及其与患者临床特征的关系。方法选取肺结核患者30例(肺结核组)和20例健康体检者(健康对照组),通过流式细胞术检测2组外周血淋巴细胞CD4^(+)CD25^(+)CD127^(low)Treg细胞的阳性率,以及检测BTLA/HVEM在肺结核患者外周血和淋巴细胞上的表达;利用蛋白芯片法检测结核抗体;通过影像检测结果判断肺结核进展程度;采用罗氏培养法培养结核分枝杆菌。结果结核组CD4^(+)CD25^(+)CD127^(low)Treg所占比例为(9.14±2.66)%,健康对照组CD4^(+)CD25^(+)CD127^(low)Treg所占比例为(6.39±1.73)%,相对于健康对照组,肺结核组患者外周血中CD4^(+)CD25^(+)CD127^(low)Treg比率明显增高;健康对照组CD4^(+)CD25^(+)CD127^(low)Treg上BTLA和HVEM的表达率高于肺结核组;BTLA、HVEM在肺结核组患者CD4^(+)CD25^(+)CD127^(low)Treg上的表达呈正相关;BTLA、HVEM在CD4^(+)CD25^(+)CD127^(low)Treg上的表达在痰涂阳性患者组中更低,而与其他临床特征无关。结论肺结核患者体内的CD4^(+)CD25^(+)CD127^(low)Treg增高,可能是抗结核免疫应答被抑制的原因,提示过度扩增导致数量异常增高的Treg是免疫应答不足和MTB逃逸的一个重要因素。负性共刺激信号BTLA/HVEM在结核患者体内下调提示其参与对CD4^(+)CD25^(+)CD127^(low)Treg的增殖的抑制作用。展开更多
变应性疾病被视为遗传和环境因素交互作用引起的炎症性疾病。近几十年来变应性疾病流行率的增高被认为与生活环境的改变有关。卫生假说指出,由于所接触病原微生物的减少,导致抑制变态反应的因素减弱,使人类正常的免疫平衡体系发生了紊...变应性疾病被视为遗传和环境因素交互作用引起的炎症性疾病。近几十年来变应性疾病流行率的增高被认为与生活环境的改变有关。卫生假说指出,由于所接触病原微生物的减少,导致抑制变态反应的因素减弱,使人类正常的免疫平衡体系发生了紊乱。本文综述了与变应性疾病发生有关的分子和细胞免疫机制。这些机制包括天然免疫刺激减弱导致的 T 细胞免疫球蛋白黏蛋白区域分子表达的改变.辅助性 T 细胞1、2型平衡的改变和调节性T细胞平衡的改变等多种因素。展开更多
基金Supported by project of National Natural Science Foundation of ChinaNo.81260595 and No.81460679+3 种基金Chinese Scholarship Council and Jiangxi province as visiting scholarNo.201408360106 and No.201408360110project of Jiangxi University of Traditional Chinese MedicineNo.JZYC15S13
文摘AIM: To explore the probable pathway by which curcumin(Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells(DCs).METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine(Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4+CD25+Foxp3+ T cells(Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules(CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur.CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease.
基金supported by a grant from National Natural Sciences Foundation of China (No.30600573)
文摘CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity.
基金supported by grants from the National Natural Science Foundation of China(No.30870584,No.81201737)the Doctoral Program Foundation of Institutions of Higher Education of China(No.20120061110063)
文摘Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line （EL-4 cells） was used. The expressions of CD4, CD25, Nrpl, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-131, IL-10, PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation, the expression of Nrpl increased significantly in 4.0 Gy group, compared with sham-irradiation group （P〈0.05） in the spleen and thymus, respectively, when ICR mice received whole-body irradiation （WBI）. Meanwhile the synthesis of Interleukin 10 （IL-20） and transforming growth factor-β1 （TGF-β1） increased significantly after high dose irradiation （HDR） （〉 or = 1.0 Gy）. In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4＋CD25＋Nrpl＋Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4＋CD25＋Nrpl＋Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.
文摘目的研究B、T淋巴细胞衰减因子(B and T lymphocyte attenuator,BTLA)及其配体疱疹病毒进入中介体(herpesvirus entry mediator,HVEM)在肺结核患者CD4^(+)CD25^(+)CD127^(low)调节性T细胞(CD4^(+)CD25^(+)CD127^(low)Treg)中的表达及其与患者临床特征的关系。方法选取肺结核患者30例(肺结核组)和20例健康体检者(健康对照组),通过流式细胞术检测2组外周血淋巴细胞CD4^(+)CD25^(+)CD127^(low)Treg细胞的阳性率,以及检测BTLA/HVEM在肺结核患者外周血和淋巴细胞上的表达;利用蛋白芯片法检测结核抗体;通过影像检测结果判断肺结核进展程度;采用罗氏培养法培养结核分枝杆菌。结果结核组CD4^(+)CD25^(+)CD127^(low)Treg所占比例为(9.14±2.66)%,健康对照组CD4^(+)CD25^(+)CD127^(low)Treg所占比例为(6.39±1.73)%,相对于健康对照组,肺结核组患者外周血中CD4^(+)CD25^(+)CD127^(low)Treg比率明显增高;健康对照组CD4^(+)CD25^(+)CD127^(low)Treg上BTLA和HVEM的表达率高于肺结核组;BTLA、HVEM在肺结核组患者CD4^(+)CD25^(+)CD127^(low)Treg上的表达呈正相关;BTLA、HVEM在CD4^(+)CD25^(+)CD127^(low)Treg上的表达在痰涂阳性患者组中更低,而与其他临床特征无关。结论肺结核患者体内的CD4^(+)CD25^(+)CD127^(low)Treg增高,可能是抗结核免疫应答被抑制的原因,提示过度扩增导致数量异常增高的Treg是免疫应答不足和MTB逃逸的一个重要因素。负性共刺激信号BTLA/HVEM在结核患者体内下调提示其参与对CD4^(+)CD25^(+)CD127^(low)Treg的增殖的抑制作用。
文摘变应性疾病被视为遗传和环境因素交互作用引起的炎症性疾病。近几十年来变应性疾病流行率的增高被认为与生活环境的改变有关。卫生假说指出,由于所接触病原微生物的减少,导致抑制变态反应的因素减弱,使人类正常的免疫平衡体系发生了紊乱。本文综述了与变应性疾病发生有关的分子和细胞免疫机制。这些机制包括天然免疫刺激减弱导致的 T 细胞免疫球蛋白黏蛋白区域分子表达的改变.辅助性 T 细胞1、2型平衡的改变和调节性T细胞平衡的改变等多种因素。
