哮喘患者过敏原刺激后气道树突状细胞的IL-25受体表达
2016/08/08
摘要
原理：白介素25（Interleukin-25 ,IL-25）是一种上皮来源的细胞因子，它的效应通过IL-25受体（IL-17RB）介导。IL-25同时被认为与过敏性疾病和气道病毒反应的病理机制有关。气道髓样树突状细胞（mDCs）和浆细胞样树突状细胞（pDCs）是专门的过敏原提呈细胞。浆细胞样树突状细胞在哮喘中发挥保护作用，同时通过Toll样受体（TLR）对微生物的识别功能在自然免疫反应中发挥关键作用。吸入过敏原对髓样和浆细胞样树突状细胞IL-17RB表达的影响及IL-25对浆细胞样树突状细胞的效应并不清楚。
目的：评估过敏原吸入引起的髓样和浆细胞样树突状细胞IL-17RB表达的变化及探索IL-25对浆细胞样树突状细胞的效应。
方法：吸入过敏原激发轻度过敏性哮喘患者（13例）。对血和痰中树突状细胞进行计数并通过流式细胞学技术在过敏原激发前、7小时后及24小时后检测L-17RB的表达。也对IL-25对浆细胞样树突状细胞的效应在体外实验中进行评估。
结果：吸入过敏原显著增加痰而并非血中髓样和浆细胞样树突状细胞数目。IL-17RB+髓样和浆细胞样树突状细胞百分比在过敏原激发24小时后在血和痰中都显著增加。IL-25上调浆细胞样树突状细胞TLR9的表达同时提升浆细胞样树突状细胞对TLR9结合体的反应。
结论：在过敏原吸入后血和痰中的髓样和浆细胞样树突状细胞上IL-17RB表达上调。IL-25通过其对TLR9表达的效应调控浆细胞样树突状细胞的功能。
Interleukin 25 receptor expression on airway dendritic cells after allergen challenge in asthmatic subjects.
Damian Tworek1,2, Steven G. Smith1, Brittany M. Salter1,Adrian J. Baatjes1, Tara Scime 1, Rick Watson1, Caitlin Obminski1,Gail M. Gauvreau1, Paul M. O’Byrne1
Am J Respir Crit Care Med. 2016; Articles in Press.
Abstract
Rationale: Interleukin (IL)-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and which has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLR). The effects of inhaled allergens on the expression of IL-17RB by mDCs and pDCs, as well as the effects of IL-25 on pDCs, are unknown.
Objective: To evaluate allergen-induced changes in IL-17RB expression by mDCs and pDCs and to investigate the effects of IL-25 on pDCs.
Methods: Patients with mild atopic asthma (n=13) were challenged with inhaled allergen. Blood and sputum DCs were enumerated and IL17-RB expression was determined by flow cytometry before, 7 and 24 hours after allergen challenge. The effects of IL-25 on pDCs in vitro were also assessed.
Results: Inhaled allergen significantly increased both mDC and pDC numbers in sputum, but not in blood. The percentage of IL-17RB+ mDCs and pDCs was significantly increased in both blood and sputum, 24 hours after challenge. IL-25 upregulated TLR9 expression by pDCs and orchestrated the responses to TLR9 ligation.
Conclusions: IL-17RB is upregulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.
原理：白介素25（Interleukin-25 ,IL-25）是一种上皮来源的细胞因子，它的效应通过IL-25受体（IL-17RB）介导。IL-25同时被认为与过敏性疾病和气道病毒反应的病理机制有关。气道髓样树突状细胞（mDCs）和浆细胞样树突状细胞（pDCs）是专门的过敏原提呈细胞。浆细胞样树突状细胞在哮喘中发挥保护作用，同时通过Toll样受体（TLR）对微生物的识别功能在自然免疫反应中发挥关键作用。吸入过敏原对髓样和浆细胞样树突状细胞IL-17RB表达的影响及IL-25对浆细胞样树突状细胞的效应并不清楚。
目的：评估过敏原吸入引起的髓样和浆细胞样树突状细胞IL-17RB表达的变化及探索IL-25对浆细胞样树突状细胞的效应。
方法：吸入过敏原激发轻度过敏性哮喘患者（13例）。对血和痰中树突状细胞进行计数并通过流式细胞学技术在过敏原激发前、7小时后及24小时后检测L-17RB的表达。也对IL-25对浆细胞样树突状细胞的效应在体外实验中进行评估。
结果：吸入过敏原显著增加痰而并非血中髓样和浆细胞样树突状细胞数目。IL-17RB+髓样和浆细胞样树突状细胞百分比在过敏原激发24小时后在血和痰中都显著增加。IL-25上调浆细胞样树突状细胞TLR9的表达同时提升浆细胞样树突状细胞对TLR9结合体的反应。
结论：在过敏原吸入后血和痰中的髓样和浆细胞样树突状细胞上IL-17RB表达上调。IL-25通过其对TLR9表达的效应调控浆细胞样树突状细胞的功能。
(张欣1 张丽1 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med. 2016; Articles in Press.）
（Am J Respir Crit Care Med. 2016; Articles in Press.）
Interleukin 25 receptor expression on airway dendritic cells after allergen challenge in asthmatic subjects.
Damian Tworek1,2, Steven G. Smith1, Brittany M. Salter1,Adrian J. Baatjes1, Tara Scime 1, Rick Watson1, Caitlin Obminski1,Gail M. Gauvreau1, Paul M. O’Byrne1
Am J Respir Crit Care Med. 2016; Articles in Press.
Abstract
Rationale: Interleukin (IL)-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and which has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLR). The effects of inhaled allergens on the expression of IL-17RB by mDCs and pDCs, as well as the effects of IL-25 on pDCs, are unknown.
Objective: To evaluate allergen-induced changes in IL-17RB expression by mDCs and pDCs and to investigate the effects of IL-25 on pDCs.
Methods: Patients with mild atopic asthma (n=13) were challenged with inhaled allergen. Blood and sputum DCs were enumerated and IL17-RB expression was determined by flow cytometry before, 7 and 24 hours after allergen challenge. The effects of IL-25 on pDCs in vitro were also assessed.
Results: Inhaled allergen significantly increased both mDC and pDC numbers in sputum, but not in blood. The percentage of IL-17RB+ mDCs and pDCs was significantly increased in both blood and sputum, 24 hours after challenge. IL-25 upregulated TLR9 expression by pDCs and orchestrated the responses to TLR9 ligation.
Conclusions: IL-17RB is upregulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.
