Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Clin Exp Allergy. 2018 Apr;48(4):379-393. doi: 10.1111/cea.13081. Epub 2018 Feb 2.
Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T-helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear.
We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2 priming after allergen exposure, using an ovalbumin-induced asthma mouse model.
Sex-based differences in the number of DCs at inflamed sites, costimulatory molecule expression on DCs, and the ability of DCs to differentiate naïve CD4 T cells into Th2 population were evaluated after allergen exposure in asthmatic mice. In addition, we assessed the role of 17β-oestradiol in CD103 DC function during Th2 priming in vitro.
The number of CD11b DCs and CD103 DCs in the lung and bronchial lymph node (BLN) was increased to a greater extent in female mice than in male mice at 16 to 20 hours after ovalbumin (OVA) inhalation. In BLNs, CD86 and I-A/I-E expression levels and antigen uptake ability in CD103 DCs, but not in CD11b DCs, were greater in female mice than in male mice. Furthermore, CD4 T cells cultured with CD103 DCs from female mice produced higher levels of interleukin (IL)-4, IL-5, and IL-13, compared with CD4 T cells cultured with CD103 DCs from male mice. The 17β-oestradiol-oriented enhancement of CD86 expression on CD103 DCs after allergen exposure induced the enhanced IL-5 production from CD4 T cells.
These findings suggest that with regard to asthma, enhanced Th2 cytokine production in females might be attributed to 17β-oestradiol-mediated Th2-oriented CD103 DCs in the BLN.
成人哮喘患者中存在性别差异，表现在其患病率和严重程度方面，这主要是由于女性患者体内的 2 型 T 辅助（Th2）细胞因子产生增强，而男性患者则不然。然而，介导这种效应的途径尚不清楚。
我们旨在通过卵清蛋白诱导的哮喘小鼠模型，确定两种主要树突状细胞（DC）亚群在女性中的作用，特别是那些在过敏原暴露后增强 Th2 启动时显示 CD11b 或 CD103 的 DC 亚群。
在哮喘小鼠中，评估过敏原暴露后炎症部位 DC 数量、DC 表面共刺激分子表达以及 DC 将幼稚 CD4 T 细胞分化为 Th2 细胞的能力方面的性别差异。此外，我们评估了 17β-雌二醇在体外 Th2 启动过程中对 CD103 DC 功能的作用。
在卵清蛋白（OVA）吸入后 16 至 20 小时，雌性小鼠肺部和支气管淋巴结（BLN）中的 CD11b DC 和 CD103 DC 数量增加得更为明显。在 BLN 中，与雄性小鼠相比，雌性小鼠的 CD103 DC 中 CD86 和 I-A/I-E 的表达水平和抗原摄取能力更高，但 CD11b DC 中没有这种情况。此外，与雄性小鼠来源的 CD103 DC 培养的 CD4 T 细胞相比，与雌性小鼠来源的 CD103 DC 培养的 CD4 T 细胞产生了更高水平的白细胞介素（IL）-4、IL-5 和 IL-13。过敏原暴露后，17β-雌二醇对 CD103 DC 上 CD86 表达的定向增强诱导了 CD4 T 细胞中 IL-5 的产生增加。
这些发现表明，就哮喘而言，女性中 Th2 细胞因子产生增强可能归因于 BLN 中 17β-雌二醇介导的 Th2 定向 CD103 DC。
