老年哮喘患者FoxP3、GATA-3和T-bet的表达
2011/03/24
摘要
背景：哮喘是一种慢性炎症性疾病，其中，Th2、Th1和抑制性T细胞(Tregs)起到重要作用。转录因子FoxP3在Treg分化中具有重要作用，而T-bet在Th1、GATA-3在Th2细胞由幼稚T细胞进行的分化中起到重要作用。近期的数据显示，年龄相关的Treg细胞下调参与了衰老对一些慢性疾病的影响。因此有必要了解老年哮喘患者中这些细胞群的变化。
目的：评价老年哮喘患者和年龄匹配的健康受试者，外周血单核细胞在基线状态及体外活化后，FoxP3、GATA-3和T-bet的基因表达情况。
方法：32名老年哮喘患者和17名年龄匹配的健康受试者入选本研究。检测血清总IgE。分离外周血单核细胞(PBMCs)，并在体外采用anti-CD3/anti-CD28抗体刺激，随后分离mRNA。反转录后，采用实时定量PCR检测相对表达。
结果：FoxP3、GATA-3和T-bet 的表达在对照组和哮喘组分别为10.2 ± 6.8 vs. 4.8 ± 3.8；2.4 ± 2.9 vs. 1.7 ± 0.9；3.3 ± 2.1 vs. 2.1 ± 1.5。与哮喘患者相比，健康者FoxP3和T-bet表达显著增加。哮喘患者具有较低的T-bet/GATA-3比例、较高的血清IgE，而且血清总IgE与GATA-3表达成明显正相关。
结论与临床相关性：老年哮喘患者，外周血单核细胞具有较低的FoxP3表达，这可能与持续的炎症和Treg细胞的免疫耐受下降相关。T-bet缺陷、GATA-3表达与IgE增加存在相关性，是持续哮喘的一个特征。与免疫衰老相关的变化可能解释哮喘患者与健康个体之间细小的差异。有必要研究老年患者持续哮喘的持续调节及其未来的治疗手段。
（刘国梁 审校）
Clin Exp Allergy. 2010 Nov 28. doi: 10.1111/j.1365-2222.2010.03640.x. [Epub ahead of print]
FoxP3, GATA-3 and T-bet expression in elderly asthma.
Vale-Pereira S, Todo-Bom A, Geraldes L, Schmidt-Weber C, Akdis CA, Mota-Pinto A.
Abstract
Background Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation while T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients. Objective To evaluate FoxP3, GATA-3 and T-bet gene expression under basal conditions and after in vitro activation in a group of elderly asthmatic compared with age-matched healthy individuals. Methods Thirty-two elderly asthmatics and 17 healthy elderly individuals were selected. Serum total IgE was measured, and peripheral blood mononuclear cells (PBMCs) were isolated and stimulated in vitro with anti-CD3/anti-CD28, followed by mRNA isolation. After reverse transcription, real-time quantitative PCR was performed and relative quantification was determined (2(-ΔΔ) (Ct) method). Results The mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2 ± 6.8 vs. 4.8 ± 3.8, 2.4 ± 2.9 vs. 1.7 ± 0.9 and 3.3 ± 2.1 vs. 2.1 ± 1.5, respectively. Healthy individuals showed significantly higher expression of FoxP3 and T-bet; asthmatics had a lower T-bet/GATA-3 ratio, higher serum IgE and a positive significant correlation between total IgE and GATA-3 expression. Conclusion and clinical relevance Elderly asthmatic patients have lower FoxP3 mRNA expression in PBMC, which can be associated with the sustained inflammatory process and with the decreased immune tolerance by Treg cells. The T-bet deficiency and the correlation of GATA-3 expression with the increase of IgE are characteristics of long-lasting asthma. Changes related to the immunosenescence process could provide an explanation for the minor differences observed between the groups. It is important to clarify persistent modifications in long-lasting asthma in the elderly and adequate future therapeutic approaches.
Clin Exp Allergy. 2010 Nov 28. doi: 10.1111/j.1365-2222.2010.03640.x. [Epub ahead of print]
背景：哮喘是一种慢性炎症性疾病，其中，Th2、Th1和抑制性T细胞(Tregs)起到重要作用。转录因子FoxP3在Treg分化中具有重要作用，而T-bet在Th1、GATA-3在Th2细胞由幼稚T细胞进行的分化中起到重要作用。近期的数据显示，年龄相关的Treg细胞下调参与了衰老对一些慢性疾病的影响。因此有必要了解老年哮喘患者中这些细胞群的变化。
目的：评价老年哮喘患者和年龄匹配的健康受试者，外周血单核细胞在基线状态及体外活化后，FoxP3、GATA-3和T-bet的基因表达情况。
方法：32名老年哮喘患者和17名年龄匹配的健康受试者入选本研究。检测血清总IgE。分离外周血单核细胞(PBMCs)，并在体外采用anti-CD3/anti-CD28抗体刺激，随后分离mRNA。反转录后，采用实时定量PCR检测相对表达。
结果：FoxP3、GATA-3和T-bet 的表达在对照组和哮喘组分别为10.2 ± 6.8 vs. 4.8 ± 3.8；2.4 ± 2.9 vs. 1.7 ± 0.9；3.3 ± 2.1 vs. 2.1 ± 1.5。与哮喘患者相比，健康者FoxP3和T-bet表达显著增加。哮喘患者具有较低的T-bet/GATA-3比例、较高的血清IgE，而且血清总IgE与GATA-3表达成明显正相关。
结论与临床相关性：老年哮喘患者，外周血单核细胞具有较低的FoxP3表达，这可能与持续的炎症和Treg细胞的免疫耐受下降相关。T-bet缺陷、GATA-3表达与IgE增加存在相关性，是持续哮喘的一个特征。与免疫衰老相关的变化可能解释哮喘患者与健康个体之间细小的差异。有必要研究老年患者持续哮喘的持续调节及其未来的治疗手段。
（刘国梁 审校）
Clin Exp Allergy. 2010 Nov 28. doi: 10.1111/j.1365-2222.2010.03640.x. [Epub ahead of print]
FoxP3, GATA-3 and T-bet expression in elderly asthma.
Vale-Pereira S, Todo-Bom A, Geraldes L, Schmidt-Weber C, Akdis CA, Mota-Pinto A.
Abstract
Background Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation while T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients. Objective To evaluate FoxP3, GATA-3 and T-bet gene expression under basal conditions and after in vitro activation in a group of elderly asthmatic compared with age-matched healthy individuals. Methods Thirty-two elderly asthmatics and 17 healthy elderly individuals were selected. Serum total IgE was measured, and peripheral blood mononuclear cells (PBMCs) were isolated and stimulated in vitro with anti-CD3/anti-CD28, followed by mRNA isolation. After reverse transcription, real-time quantitative PCR was performed and relative quantification was determined (2(-ΔΔ) (Ct) method). Results The mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2 ± 6.8 vs. 4.8 ± 3.8, 2.4 ± 2.9 vs. 1.7 ± 0.9 and 3.3 ± 2.1 vs. 2.1 ± 1.5, respectively. Healthy individuals showed significantly higher expression of FoxP3 and T-bet; asthmatics had a lower T-bet/GATA-3 ratio, higher serum IgE and a positive significant correlation between total IgE and GATA-3 expression. Conclusion and clinical relevance Elderly asthmatic patients have lower FoxP3 mRNA expression in PBMC, which can be associated with the sustained inflammatory process and with the decreased immune tolerance by Treg cells. The T-bet deficiency and the correlation of GATA-3 expression with the increase of IgE are characteristics of long-lasting asthma. Changes related to the immunosenescence process could provide an explanation for the minor differences observed between the groups. It is important to clarify persistent modifications in long-lasting asthma in the elderly and adequate future therapeutic approaches.
Clin Exp Allergy. 2010 Nov 28. doi: 10.1111/j.1365-2222.2010.03640.x. [Epub ahead of print]
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营养素和食物在哮喘与过敏症初级预防中的作用：系统综述与荟萃分析
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