Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma
Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma
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DOI：
10.1016/j.jaci.2004.07.014
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发表时间：
2004-12-01
影响因子：
14.2
通讯作者：
Schmidt-Weber, CB
中科院分区：
文献类型：
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作者：
Karagiannidis, C;Akdis, M;Schmidt-Weber, CB
背景：调节性T细胞（T-reg）的特征是表达抑制性细胞因子和转录因子FOXP 3。它们在平衡免疫反应和维持对抗原和过敏原的外周耐受性方面发挥关键作用。外周对变应原耐受性的丧失导致的疾病可以用糖皮质激素治疗控制。目的：本研究基于FOXP 3和细胞因子表达来探讨糖皮质激素是否影响T-reg细胞的活性。从健康供体和糖皮质激素治疗的哮喘患者中分离出CD 4（+）T细胞，并检测FOXP 3、沿着IL-10和TGF-β 1的表达，确定了结果：哮喘患者接受吸入性糖皮质激素治疗、全身性糖皮质激素治疗或两者联合治疗后，FOXP 3 mRNA表达显著增加，而哮喘患者接受吸入性糖皮质激素治疗后，FOXP 3 mRNA表达显著增加。FOXP 3与IL 10 mRNA表达密切相关。FOXP 3 mRNA表达与染色体Xp11.23上的（GT）n微卫星启动子多态性或总IgE水平无关。全身性糖皮质激素治疗后，CD 25（+）记忆性CD 4（+）T细胞的频率和CD 4（+）T细胞瞬时FOXP 3 mRNA表达显著增加，而TGFBI表达无变化。结论：糖皮质激素治疗不仅具有免疫抑制作用，而且通过FOXP 3依赖的机制促进或启动T（R）1细胞向T（R）1细胞分化。将短暂的糖皮质激素诱导的T-reg活性转化为稳定表型的策略可能会改善过敏和哮喘治疗。
Background: T regulatory (T-reg) cells are characterized by expression of suppressive cytokines and the transcription factor FOXP3. They play a key role in balancing immune responses and maintain peripheral tolerance against antigens and allergens. The loss of peripheral tolerance against allergens causes diseases that can be therapeutically controlled with glucocorticoids.Objective: The present study investigates whether glucocorticoids affect the activity of T-reg cells on the basis of FOXP3 and cytokine expression.Methods: CD4(+) T cells from healthy donors and glucocorticoid-treated asthmatic patients were isolated, and expression of FOXP3, along with IL-10 and TGF-beta1, was determined. The effect of glucocorticoids on Treg cells was measured in vivo before and after GC treatment and in in vitro cultures.Results: FOXP3 mRNA expression was significantly increased in asthmatic patients receiving inhaled glucocorticoid treatment, systemic glucocorticoid treatment, or both. FOXP3 tightly correlated with IL10 mRNA expression. No correlation of FOXP3 mRNA expression was observed in relation to a (GT)n microsatellite promoter polymorphism on chromosome Xp11.23 or total IgE level. The frequency of CD25(+) memory CD4(+) T cells and transient FOXP3 mRNA expression by CD4(+) T cells significantly increased after systemic glucocorticoid treatment, whereas TGFBI expression did not change. Furthermore, glucocorticoids induced IL10 and FOXP3 expression in short-term and long-term cultures in vitro.Conclusion: These findings demonstrate that glucocorticoid treatment is not only immunosuppressive and antiinflammatory but also promotes or initiates differentiation toward T(R)1 cells by a FOXP3-dependent mechanism. Strategies that convert transient glucocorticoid-induced T-reg activity into a stable phenotype might improve allergy and asthma therapy.