性别差异：CD103+树突状细胞在过敏性哮喘促进女性为主Th2细胞因子生成
2018/01/15
摘要
背景：成人哮喘在发病率和严重程度上存在性别差异，其主要归因于女性患者Th2细胞因子生成显著多于男性患者。然而，介导这一效应的通路尚不明确。
目的：本研究旨在评价女性患者树突状细胞（DCs）两个组要亚型的作用，尤其是在OVA诱导哮喘小鼠模型中给予过敏原刺激后表达CD11b 或CD103的DCs。
方法：在哮喘小鼠模型中给予过敏原刺激后，性别差异性表现在炎症区域DCs数量，联合刺激分子表达，幼稚CD4+T细胞向Th2转化的分化能力。此外，体外研究评估Th2启动过程中17β-雌二醇在CD103+DC的作用。
结果：在OVA吸入16-20小时后，雌性小鼠肺和支气管淋巴结（BLN）CD11b高表达DCs和CD103+DCs显著高于雄性小鼠。在BLN中，CD86和I-A/I-E表达水平和抗原提成能力在雌性小鼠中显著高于雄性小鼠，但在CD11b高表达DCs中未有类似情况。此外，与CD103+DCs共培养CD4+T细胞中，雌性小鼠较雄性小鼠IL-4、IL-5和IL-13生成增加。在过敏原暴露后，17β雌二醇导致CD103+DCs中CD86表达增加，进而诱导CD4+T细胞中IL-5生成增加。
结论&临床意义：本研究提示在哮喘中，女性Th2细胞因子生成增加可能与BLN中17β雌二醇介导Th2诱导CD103+DCs相关。
Sex-based differences in CD103+ dendritic cells promote female-predominant Th2 cytokine production during allergic asthma.
Clin Exp Allergy. 2017 Dec 30. doi: 10.1111/cea.13081. [Epub ahead of print]
Masuda C, Miyasaka T, Kawakami K, Inokuchi JI, Kawano T, Dobashi-Okuyama K, Takahashi T, Takayanagi M, Ohno I.
Abstract
BACKGROUND: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.
OBJECTIVE: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.
METHODS:Sex-based differences in the number of DCs at inflamed sites, co-stimulatory 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-estradiol in CD103+ DC function during Th2-priming in vitro.
RESULTS:The number of CD11bhigh DCs and CD103+ DCs in the lung and bronchial lymph node (BLN) were 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 CD11bhigh 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-estradiol oriented-enhancement of CD86 expression on CD103+ DCs after allergen exposure induced the enhanced IL-5 production from CD4+ T cells.
CONCLUSIONS & CLINICAL RELEVANCE:These findings suggest that with regards to asthma, enhanced Th2 cytokine production in females might be attributed to 17β-estradiol-mediated Th2-oriented CD103+ DCs in the BLN.
背景：成人哮喘在发病率和严重程度上存在性别差异，其主要归因于女性患者Th2细胞因子生成显著多于男性患者。然而，介导这一效应的通路尚不明确。
目的：本研究旨在评价女性患者树突状细胞（DCs）两个组要亚型的作用，尤其是在OVA诱导哮喘小鼠模型中给予过敏原刺激后表达CD11b 或CD103的DCs。
方法：在哮喘小鼠模型中给予过敏原刺激后，性别差异性表现在炎症区域DCs数量，联合刺激分子表达，幼稚CD4+T细胞向Th2转化的分化能力。此外，体外研究评估Th2启动过程中17β-雌二醇在CD103+DC的作用。
结果：在OVA吸入16-20小时后，雌性小鼠肺和支气管淋巴结（BLN）CD11b高表达DCs和CD103+DCs显著高于雄性小鼠。在BLN中，CD86和I-A/I-E表达水平和抗原提成能力在雌性小鼠中显著高于雄性小鼠，但在CD11b高表达DCs中未有类似情况。此外，与CD103+DCs共培养CD4+T细胞中，雌性小鼠较雄性小鼠IL-4、IL-5和IL-13生成增加。在过敏原暴露后，17β雌二醇导致CD103+DCs中CD86表达增加，进而诱导CD4+T细胞中IL-5生成增加。
结论&临床意义：本研究提示在哮喘中，女性Th2细胞因子生成增加可能与BLN中17β雌二醇介导Th2诱导CD103+DCs相关。
（上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（Clin Exp Allergy. 2017 Dec 30. doi: 10.1111/cea.13081. [Epub ahead of print]）
（Clin Exp Allergy. 2017 Dec 30. doi: 10.1111/cea.13081. [Epub ahead of print]）
Sex-based differences in CD103+ dendritic cells promote female-predominant Th2 cytokine production during allergic asthma.
Clin Exp Allergy. 2017 Dec 30. doi: 10.1111/cea.13081. [Epub ahead of print]
Masuda C, Miyasaka T, Kawakami K, Inokuchi JI, Kawano T, Dobashi-Okuyama K, Takahashi T, Takayanagi M, Ohno I.
Abstract
BACKGROUND: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.
OBJECTIVE: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.
METHODS:Sex-based differences in the number of DCs at inflamed sites, co-stimulatory 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-estradiol in CD103+ DC function during Th2-priming in vitro.
RESULTS:The number of CD11bhigh DCs and CD103+ DCs in the lung and bronchial lymph node (BLN) were 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 CD11bhigh 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-estradiol oriented-enhancement of CD86 expression on CD103+ DCs after allergen exposure induced the enhanced IL-5 production from CD4+ T cells.
CONCLUSIONS & CLINICAL RELEVANCE:These findings suggest that with regards to asthma, enhanced Th2 cytokine production in females might be attributed to 17β-estradiol-mediated Th2-oriented CD103+ DCs in the BLN.
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