Matsumoto Koichiro, Inoue Hiromasa, Fukuyama Satoru, Kan-O Keiko, Eguchi-Tsuda Miyuki, Matsumoto Takafumi, Moriwaki Atsushi, Nakano Takako, Nakanishi Yoichi
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Respirology. 2009 Mar;14(2):187-94. doi: 10.1111/j.1440-1843.2008.01472.x. Epub 2009 Jan 23.
A forkhead/winged-helix family transcriptional repressor, Foxp3, is highly expressed on CD4(+)CD25(+) T regulatory cells. The role of Foxp3(+)CD4(+)CD25(+) T regulatory cells in asthma remains to be elucidated. Using mouse models and peripheral blood mononuclear cells (PBMC) from subjects with allergic asthma, we aimed to explore whether Foxp3(+)CD4(+)CD25(+) T regulatory cells associate with asthma phenotypes.
Foxp3(+)CD4(+)CD25(+) T cells were detected by FACS and the correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma phenotypes was assessed.
The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in the lungs showed an inverse correlation with eosinophilic inflammation in BALB/c, A/J and C57BL/6 strains. In addition, the frequency of Foxp3(+)CD4(+)CD25(+) T cells was inversely correlated with BHR and allergen-specific IgE levels in the serum of A/J mice. In BALB/c mice, the frequency of Foxp3(+)CD4(+)CD25(+) T cells correlated with the level of IL-10 in BAL fluid. The inverse correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and eosinophilic inflammation disappeared when mice were treated with anti-IL-10 receptor mAb during allergen challenge. Interestingly, intracellular cytokine staining of lung cells revealed that IL-10 was predominantly produced by Foxp3(-)CD4(+)CD25(+) T cells. The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in PBMC of asthmatics was significantly lower than that of healthy subjects, although there was no significant correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma severity.
These results suggest a role for lung Foxp3(+)CD4(+)CD25(+) T cells in the regulation of asthma phenotypes, presumably through an IL-10-mediated mechanism.
一种叉头框/翼状螺旋家族转录抑制因子Foxp3，在CD4(+)CD25(+)调节性T细胞上高表达。Foxp3(+)CD4(+)CD25(+)调节性T细胞在哮喘中的作用仍有待阐明。我们利用小鼠模型以及过敏性哮喘患者的外周血单个核细胞（PBMC），旨在探究Foxp3(+)CD4(+)CD25(+)调节性T细胞是否与哮喘表型相关。
通过流式细胞术检测Foxp3(+)CD4(+)CD25(+)T细胞，并评估Foxp3(+)CD4(+)CD25(+)T细胞频率与哮喘表型之间的相关性。
在BALB/c、A/J和C57BL/6品系小鼠的肺中，总CD4(+)CD25(+)T细胞中Foxp3(+)CD4(+)CD25(+)T细胞的频率与嗜酸性粒细胞炎症呈负相关。此外，A/J小鼠血清中Foxp3(+)CD4(+)CD25(+)T细胞的频率与气道高反应性（BHR）及变应原特异性IgE水平呈负相关。在BALB/c小鼠中，Foxp3(+)CD4(+)CD25(+)T细胞的频率与支气管肺泡灌洗液（BAL液）中IL-10的水平相关。当在变应原激发期间用抗IL-10受体单克隆抗体治疗小鼠时，Foxp3(+)CD4(+)CD25(+)T细胞频率与嗜酸性粒细胞炎症之间的负相关消失。有趣的是，肺细胞的细胞内细胞因子染色显示IL-10主要由Foxp3(-)CD4(+)CD25(+)T细胞产生。哮喘患者PBMC中总CD4(+)CD25(+)T细胞中Foxp3(+)CD4(+)CD25(+)T细胞的频率显著低于健康受试者，尽管Foxp3(+)CD4(+)CD25(+)T细胞频率与哮喘严重程度之间无显著相关性。
这些结果表明肺中Foxp3(+)CD4(+)CD25(+)T细胞在调节哮喘表型中发挥作用，可能是通过IL-10介导的机制。
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