TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway.
TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway.
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DOI：
10.1186/1710-1492-6-4
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Nadeau KC
中科院分区：
文献类型：
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作者：
Nguyen KD;Vanichsarn C;Nadeau KC
尽管胸腺间质淋巴生成素(TSLP)与变态反应性炎症的发生有关，但其对调节性T细胞(Treg)介导的免疫耐受的影响尚未被探讨。我们的目的是剖析TSLP对Treg免疫抑制活性的影响及其在人类过敏性哮喘中的潜在后果。采用体外培养系统研究TSLP对人Treg的影响。通过抑制试验和流式细胞仪分析，对15名过敏性哮喘、15名健康对照和15名非过敏性哮喘受试者的肺Treg的功能能力进行了评估。活化的肺Treg表达TSLP-R，并对TSLP介导的STAT5激活有反应。TSLP直接和选择性地损伤Treg细胞产生IL-10，并抑制其抑制活性。在人类过敏性哮喘中，与健康对照组和非过敏性哮喘对应物相比，肺Treg表现出显著的抑制活性和IL-10产生。这些功能改变与过敏性哮喘患者的支气管肺泡灌洗液(BAL)中TSLP表达升高有关。此外，过敏性哮喘BAL可通过TSLP依赖的方式抑制健康对照肺Treg产生IL-10。这些结果首次为TSLP在Treg抑制活性的调节中发挥直接作用提供了证据。TSLP介导的Treg功能抑制可能为抑制炎症哮喘气道耐受性免疫反应提供了一种新的病理机制。
Even though thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation, its influence on immune tolerance mediated by regulatory T cells (Treg) have not been explored. We aimed to dissect the influence of TSLP on immunosuppressive activities of Treg and its potential consequences in human allergic asthma. In vitro culture system was utilized to study the effects of TSLP on human Treg. The functional competency of pulmonary Treg from a cohort of 15 allergic asthmatic, 15 healthy control, and 15 non-allergic asthmatic subjects was also evaluated by suppression assays and flow cytometric analysis. Activated pulmonary Treg expressed TSLP-R and responded to TSLP-mediated activation of STAT5. TSLP directly and selectively impaired IL-10 production of Treg and inhibited their suppressive activity. In human allergic asthma, pulmonary Treg exhibited a significant decrease in suppressive activity and IL-10 production compared to healthy control and non-allergic asthmatic counterparts. These functional alterations were associated with elevated TSLP expression in bronchoaveolar lavage fluid (BAL) of allergic asthmatic subjects. Furthermore, allergic asthmatic BAL could suppress IL-10 production by healthy control pulmonary Treg in a TSLP-dependent manner. These results provide the first evidences for a direct role of TSLP in the regulation of suppressive activities of Treg. TSLP mediated inhibition of Treg function might present a novel pathologic mechanism to dampen tolerogenic immune responses in inflamed asthmatic airway.