Malmhäll C, Bossios A, Pullerits T, Lötvall J
Lung Pharmacology Group, Department of Internal Medicine/Respiratory Medicine and Allergology, The Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden.
Allergy. 2007 Sep;62(9):1007-13. doi: 10.1111/j.1398-9995.2007.01420.x.
T-regulatory cells (Treg) affect the balance of T(H)2 and T(H)1 cells. Treg, T(H)2 and T(H)1 cells are regulated by the FOXP3, GATA-3 and T-bet transcription factors respectively. Our aim was to determine the number of FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa in symptom-free allergic rhinitis (AR) patients vs healthy controls, as well as the effects of natural pollen exposure and concomitant nasal glucocorticoid treatment on these cells.
Nasal biopsies were taken from healthy controls and patients with grass-pollen AR preseason. The AR patients were randomized to receive treatment with either fluticasone propionate (FP) or a placebo, and additional biopsies were taken during the pollen season. FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa were quantified by immunohistochemistry.
The number of FOXP3(+) and GATA-3(+) cells, but not T-bet(+) cells, was significantly higher in AR patients vs controls preseason. The number of FOXP3(+) cells remained unchanged in the former group after the pollen season but decreased significantly in the nasal mucosa as a result of FP treatment. The pollen season substantially increased the number of GATA-3(+) cells, which was inhibited by FP. The number of T-bet(+) cells was not affected by pollen or FP.
These data suggest that nasal glucocorticoids attenuate the allergic inflammation partly by reducing the number of T(H)2 cells, but not by means of local upregulation of Treg cells. The local relationship between T(H)1 and T(H)2 cells as well as between Treg and T(H)2 is maintained by nasal glucocorticoid treatment.
调节性T细胞(Treg)影响辅助性T细胞2(TH2)和辅助性T细胞1(TH1)的平衡。Treg、TH2和TH1细胞分别受叉头框蛋白3(FOXP3)、GATA结合蛋白3(GATA-3)和T盒转录因子(T-bet)调控。我们的目的是确定无症状性变应性鼻炎(AR)患者与健康对照者鼻黏膜中FOXP3(+)、GATA-3(+)和T-bet(+)细胞的数量,以及自然花粉暴露和鼻用糖皮质激素治疗对这些细胞的影响。
从健康对照者和草花粉AR患者季前进行鼻活检。将AR患者随机分为接受丙酸氟替卡松(FP)治疗或安慰剂治疗,并在花粉季节期间进行额外活检。通过免疫组织化学对鼻黏膜中的FOXP3(+)、GATA-3(+)和T-bet(+)细胞进行定量。
季前AR患者中FOXP3(+)和GATA-3(+)细胞数量显著高于对照组,但T-bet(+)细胞数量无差异。花粉季节后,前一组中FOXP3(+)细胞数量保持不变,但由于FP治疗,鼻黏膜中该细胞数量显著减少。花粉季节使GATA-3(+)细胞数量大幅增加,而FP可抑制这一增加。T-bet(+)细胞数量不受花粉或FP影响。
这些数据表明,鼻用糖皮质激素部分通过减少TH2细胞数量减轻变应性炎症,但并非通过局部上调Treg细胞数量。鼻用糖皮质激素治疗维持了TH1和TH2细胞之间以及Treg和TH2细胞之间的局部关系。