重症哮喘树突状细胞表型反映对糖皮质激素的临床反应性
2018/05/30
摘要
背景：重症哮喘患者的亚组尽管长期大剂量糖皮质激素治疗仍然存在症状。我们假设这些哮喘患者的临床糖皮质激素敏感性反映在外周血树突状细胞亚群的差异上。比较基线和系统性糖皮质激素（类固醇）治疗2周后用流式细胞术检测的外周血白细胞数量，以确定激素敏感（SS）和激素抵抗（SR）哮喘患者的免疫学差异。
方法：评估成人重症哮喘患者（SS n = 12; SR n = 23）对口服泼尼松龙治疗2周的反应。治疗前后取外周血并对淋巴细胞(CD3, CD19, CD4, CD8 and Foxp3) 和树突状细胞标志物 (谱系阴性[CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86)进行染色。
结果:与激素敏感哮喘患者相比，激素抵抗哮喘患者血液中观察到骨髓样树突状细胞(mDCs)而不是浆细胞样树突状细胞(pDCs)有更高的中位频率(P = 0.03)。糖皮质激素治疗显著增加B细胞的中位数，而不是两个队列中的T细胞数量，具有增加SS而不是SR受试者中的Foxp3 +调节性T细胞数量的趋势（P =0.07）。口服泼尼松龙治疗显著降低了SS和SR哮喘患者中总DCs和pDCs的中位数和中位频率。有趣的是，所有患者的pDCs中HLA-DR和ILT3的表达也降低。相反，治疗增加了SS哮喘患者中mDCs的中位频率，但在SR哮喘患者中减少。
结论：与SS哮喘患者相比，SR哮喘患者中骨髓样DCs频率升高，骨髓样DCs对口服泼尼松龙治疗有不同的反应。
Dendritic cell phenotype in severe asthma reflects clinical responsiveness to glucocorticoids..
Chambers ES1, Nanzer AM1,2, Pfeffer PE1, Richards DF1, Martineau AR2, Griffiths CJ2, Corrigan CJ1, Hawrylowicz CM1.
Abstract
BACKGROUND:Subsets of patients with severe asthma remain symptomatic despite prolonged, high-dose glucocorticoid therapy. We hypothesized that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. To compare peripheral blood leucocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid-sensitive (SS) and steroid-resistant (SR) asthmatics.
METHODS:Adult severe asthmatics (SS n = 12; SR n = 23) were assessed for their response to 2 weeks of therapy with oral prednisolone. Peripheral blood was obtained before and after therapy and stained for lymphocyte (CD3, CD19, CD4, CD8 and Foxp3) and dendritic cell markers (Lineage negative [CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86).
RESULTS:A higher median frequency of myeloid DCs (mDCs) but not plasmacytoid DCs (pDCs) was observed in the blood of SR as compared to SS asthmatics (P = .03). Glucocorticoid therapy significantly increased median B cell, but not T cell numbers in both cohorts, with a trend for increased numbers of Foxp3+ Tregs in SS (P = .07), but not SR subjects. Oral prednisolone therapy significantly reduced the median numbers and frequencies of total DCs and pDCs in both SS and SR asthmatics. Interestingly, the expression of HLA-DR and ILT3 was also reduced on pDCs in all patients. In contrast, therapy increased the median frequency of mDCs in SS, but reduced it in SR asthmatics.
CONCLUSIONS:Myeloid DC frequency is elevated in SR compared with SS asthmatics, and mDC shows a differential response to oral prednisolone therapy.
背景：重症哮喘患者的亚组尽管长期大剂量糖皮质激素治疗仍然存在症状。我们假设这些哮喘患者的临床糖皮质激素敏感性反映在外周血树突状细胞亚群的差异上。比较基线和系统性糖皮质激素（类固醇）治疗2周后用流式细胞术检测的外周血白细胞数量，以确定激素敏感（SS）和激素抵抗（SR）哮喘患者的免疫学差异。
方法：评估成人重症哮喘患者（SS n = 12; SR n = 23）对口服泼尼松龙治疗2周的反应。治疗前后取外周血并对淋巴细胞(CD3, CD19, CD4, CD8 and Foxp3) 和树突状细胞标志物 (谱系阴性[CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86)进行染色。
结果:与激素敏感哮喘患者相比，激素抵抗哮喘患者血液中观察到骨髓样树突状细胞(mDCs)而不是浆细胞样树突状细胞(pDCs)有更高的中位频率(P = 0.03)。糖皮质激素治疗显著增加B细胞的中位数，而不是两个队列中的T细胞数量，具有增加SS而不是SR受试者中的Foxp3 +调节性T细胞数量的趋势（P =0.07）。口服泼尼松龙治疗显著降低了SS和SR哮喘患者中总DCs和pDCs的中位数和中位频率。有趣的是，所有患者的pDCs中HLA-DR和ILT3的表达也降低。相反，治疗增加了SS哮喘患者中mDCs的中位频率，但在SR哮喘患者中减少。
结论：与SS哮喘患者相比，SR哮喘患者中骨髓样DCs频率升高，骨髓样DCs对口服泼尼松龙治疗有不同的反应。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校))
(Clin Exp Allergy. 2018 Jan;48(1):13-22. doi: 10.1111/cea.13061. Epub 2017 Dec 18)
(Clin Exp Allergy. 2018 Jan;48(1):13-22. doi: 10.1111/cea.13061. Epub 2017 Dec 18)
Dendritic cell phenotype in severe asthma reflects clinical responsiveness to glucocorticoids..
Chambers ES1, Nanzer AM1,2, Pfeffer PE1, Richards DF1, Martineau AR2, Griffiths CJ2, Corrigan CJ1, Hawrylowicz CM1.
Abstract
BACKGROUND:Subsets of patients with severe asthma remain symptomatic despite prolonged, high-dose glucocorticoid therapy. We hypothesized that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. To compare peripheral blood leucocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid-sensitive (SS) and steroid-resistant (SR) asthmatics.
METHODS:Adult severe asthmatics (SS n = 12; SR n = 23) were assessed for their response to 2 weeks of therapy with oral prednisolone. Peripheral blood was obtained before and after therapy and stained for lymphocyte (CD3, CD19, CD4, CD8 and Foxp3) and dendritic cell markers (Lineage negative [CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86).
RESULTS:A higher median frequency of myeloid DCs (mDCs) but not plasmacytoid DCs (pDCs) was observed in the blood of SR as compared to SS asthmatics (P = .03). Glucocorticoid therapy significantly increased median B cell, but not T cell numbers in both cohorts, with a trend for increased numbers of Foxp3+ Tregs in SS (P = .07), but not SR subjects. Oral prednisolone therapy significantly reduced the median numbers and frequencies of total DCs and pDCs in both SS and SR asthmatics. Interestingly, the expression of HLA-DR and ILT3 was also reduced on pDCs in all patients. In contrast, therapy increased the median frequency of mDCs in SS, but reduced it in SR asthmatics.
CONCLUSIONS:Myeloid DC frequency is elevated in SR compared with SS asthmatics, and mDC shows a differential response to oral prednisolone therapy.
上一篇：
重症哮喘中降低奥马珠单抗反应的因素
下一篇：
糖皮质激素治疗通过STAT通路抑制哮喘患者的ILC2的活性及活动频率
