Karagiannidis Christian, Akdis Mübeccel, Holopainen Päivi, Woolley Niina J, Hense Gabriele, Rückert Beate, Mantel Pierre-Yves, Menz Günther, Akdis Cezmi A, Blaser Kurt, Schmidt-Weber Carsten B
Swiss Institute of Allergy and Asthma Research, Davos, Switzerland.
J Allergy Clin Immunol. 2004 Dec;114(6):1425-33. doi: 10.1016/j.jaci.2004.07.014.
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.
The present study investigates whether glucocorticoids affect the activity of T reg cells on the basis of FOXP3 and cytokine expression.
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 T reg cells was measured in vivo before and after GC treatment and in in vitro cultures.
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 TGFB1 expression did not change. Furthermore, glucocorticoids induced IL10 and FOXP3 expression in short-term and long-term cultures in vitro.
These findings demonstrate that glucocorticoid treatment is not only immunosuppressive and anti-inflammatory 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.
调节性T（Treg）细胞的特征是表达抑制性细胞因子和转录因子FOXP3。它们在平衡免疫反应和维持对外源抗原及变应原的外周耐受中起关键作用。对外源变应原外周耐受的丧失会引发一些疾病，这些疾病可用糖皮质激素进行治疗控制。
本研究基于FOXP3和细胞因子表达情况，探究糖皮质激素是否会影响Treg细胞的活性。
分离健康供体和接受糖皮质激素治疗的哮喘患者的CD4+T细胞，检测FOXP3以及白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1）的表达。在糖皮质激素（GC）治疗前后的体内以及体外培养中，测定糖皮质激素对Treg细胞的影响。
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的哮喘患者，其FOXP3 mRNA表达显著增加。FOXP3与IL10 mRNA表达密切相关。未观察到FOXP3 mRNA表达与Xp11.23染色体上的（GT）n微卫星启动子多态性或总IgE水平相关。全身性糖皮质激素治疗后，CD25+记忆性CD4+T细胞的频率以及CD4+T细胞短暂的FOXP3 mRNA表达显著增加，而TGFB1表达未改变。此外，糖皮质激素在体外短期和长期培养中均可诱导IL10和FOXP3表达。
这些发现表明，糖皮质激素治疗不仅具有免疫抑制和抗炎作用，还通过FOXP3依赖机制促进或启动向Tr1细胞的分化。将短暂的糖皮质激素诱导的Treg活性转化为稳定表型的策略可能会改善变应性疾病和哮喘的治疗。
