固有淋巴细胞促成肥胖介导的过敏性气道疾病急性发作
2016/07/07
摘要
背景：流行病学与临床观察确定肥胖是哮喘急性发作的一个重要危险因素，但是其潜在的机制仍然知之甚少。已有研究证实2型与3型固有淋巴细胞（Type 2 and 3 Innate Lymphoid Cells，ILC2与ILC3）分别参与到哮喘，脂肪组织稳态和肥胖相关的气道高反应性（airway hyperresponsiveness，AHR）中。
目的：为了探索ILC在高脂饮食（high fat diet，HFD）诱导的肥胖介导的过敏性气道疾病急性发作中的潜在作用。
方法：肥胖通过HFD饲养诱导，随后过敏性气道炎症通过鼻腔内给予屋尘螨（house dust mite，HDM）提取物进行诱导。在ILC存在或缺乏情况下，分析AHR、肺和内脏脂肪组织（visceral adipose tissue，VAT）炎症、体液免疫反应、细胞因子与固有和获得性淋巴细胞群。
结果：HFD饲养加重了过敏性气道疾病特征，包括体液免疫反应、气道和组织嗜酸性粒细胞增多、AHR以及Th2和Th17相关的肺表达谱。值得注意的是，与瘦小鼠比较，非致敏肥胖小鼠在没有AHR条件下已经表现出肺ILC增多以及组织嗜酸粒细胞浸润增加。与HDM激发的瘦小鼠比较，在HDM激发的肥胖小鼠中肺ILC2与ILC3细胞总数及细胞因子表达的细胞数量进一步增加，同时伴有IL-33与IL-1β表达增加以及VAT中ILC标志物减少。此外，在肥胖小鼠中，用抗-CD90抗体封闭ILC，随后进行淋巴细胞重建，这导致了包括Th2与Th17浸润的过敏性气道炎症特征显著减少。
结论：这些结果表明HFD诱导的肥胖可能通过涉及ILC2与ILC3机制加重过敏性气道炎症。
Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity
Everaere L, Ait-Yahia S, Molendi-Coste O, Vorng H, Quemener S, LeVu P, Fleury S, Bouchaert E, Fan Y, Duez C, Patricia de Nadai, Staels B, Dombrowicz D and Tsicopoulos A
J Allergy Clin Immunol 2016 PII: S0091-6749 (16) 30017-3
Abstract
Background: Epidemiological and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 and 3 Innate Lymphoid Cells (ILC2 and ILC3) have been implicated respectively in asthma and adipose tissue homeostasis, and in obesity-associated airway hyperresponsiveness (AHR).
Objective: To determine the potential involvement of ILC in allergic airway disease exacerbation by high fat diet-(HFD) induced obesity.
Methods: Obesity was induced by HFD feeding and allergic airway inflammation was subsequently induced by intranasal administrations of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue (VAT) inflammation, humoral response, cytokine and innate and adaptive lymphoid populations were analysed in the presence or absence of ILC.
Results: HFD feeding exacerbated allergic airway disease features including humoral response, airway and tissue eosinophilia, AHR, and Th2 and Th17 pulmonary profiles. Notably, non-sensitized obese mice already exhibited increased lung ILC and tissue eosinophil infiltration compared with lean mice in the absence of AHR. The number of total and cytokine- expressing lung ILC2 and ILC3 further increased in HDM-challenged obese mice compared to HDM-challenged lean mice and was accompanied by high levels of IL-33 and IL-1β and decreased ILC markers in VAT. Furthermore, depletion of ILC with an anti-CD90 antibody, followed by T cell reconstitution, led to a profound decrease of allergic airway inflammatory features in obese mice, including Th2 and Th17 infiltration.
Conclusion: These results indicate that HFD-induced obesity may exacerbate allergic airway inflammation by mechanisms involving ILC2 and ILC3.
背景：流行病学与临床观察确定肥胖是哮喘急性发作的一个重要危险因素，但是其潜在的机制仍然知之甚少。已有研究证实2型与3型固有淋巴细胞（Type 2 and 3 Innate Lymphoid Cells，ILC2与ILC3）分别参与到哮喘，脂肪组织稳态和肥胖相关的气道高反应性（airway hyperresponsiveness，AHR）中。
目的：为了探索ILC在高脂饮食（high fat diet，HFD）诱导的肥胖介导的过敏性气道疾病急性发作中的潜在作用。
方法：肥胖通过HFD饲养诱导，随后过敏性气道炎症通过鼻腔内给予屋尘螨（house dust mite，HDM）提取物进行诱导。在ILC存在或缺乏情况下，分析AHR、肺和内脏脂肪组织（visceral adipose tissue，VAT）炎症、体液免疫反应、细胞因子与固有和获得性淋巴细胞群。
结果：HFD饲养加重了过敏性气道疾病特征，包括体液免疫反应、气道和组织嗜酸性粒细胞增多、AHR以及Th2和Th17相关的肺表达谱。值得注意的是，与瘦小鼠比较，非致敏肥胖小鼠在没有AHR条件下已经表现出肺ILC增多以及组织嗜酸粒细胞浸润增加。与HDM激发的瘦小鼠比较，在HDM激发的肥胖小鼠中肺ILC2与ILC3细胞总数及细胞因子表达的细胞数量进一步增加，同时伴有IL-33与IL-1β表达增加以及VAT中ILC标志物减少。此外，在肥胖小鼠中，用抗-CD90抗体封闭ILC，随后进行淋巴细胞重建，这导致了包括Th2与Th17浸润的过敏性气道炎症特征显著减少。
结论：这些结果表明HFD诱导的肥胖可能通过涉及ILC2与ILC3机制加重过敏性气道炎症。
(刘影1 张红萍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)
（J Allergy Clin Immunol 2016 PII: S0091-6749 (16) 30017-3）
（J Allergy Clin Immunol 2016 PII: S0091-6749 (16) 30017-3）
Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity
Everaere L, Ait-Yahia S, Molendi-Coste O, Vorng H, Quemener S, LeVu P, Fleury S, Bouchaert E, Fan Y, Duez C, Patricia de Nadai, Staels B, Dombrowicz D and Tsicopoulos A
J Allergy Clin Immunol 2016 PII: S0091-6749 (16) 30017-3
Abstract
Background: Epidemiological and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 and 3 Innate Lymphoid Cells (ILC2 and ILC3) have been implicated respectively in asthma and adipose tissue homeostasis, and in obesity-associated airway hyperresponsiveness (AHR).
Objective: To determine the potential involvement of ILC in allergic airway disease exacerbation by high fat diet-(HFD) induced obesity.
Methods: Obesity was induced by HFD feeding and allergic airway inflammation was subsequently induced by intranasal administrations of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue (VAT) inflammation, humoral response, cytokine and innate and adaptive lymphoid populations were analysed in the presence or absence of ILC.
Results: HFD feeding exacerbated allergic airway disease features including humoral response, airway and tissue eosinophilia, AHR, and Th2 and Th17 pulmonary profiles. Notably, non-sensitized obese mice already exhibited increased lung ILC and tissue eosinophil infiltration compared with lean mice in the absence of AHR. The number of total and cytokine- expressing lung ILC2 and ILC3 further increased in HDM-challenged obese mice compared to HDM-challenged lean mice and was accompanied by high levels of IL-33 and IL-1β and decreased ILC markers in VAT. Furthermore, depletion of ILC with an anti-CD90 antibody, followed by T cell reconstitution, led to a profound decrease of allergic airway inflammatory features in obese mice, including Th2 and Th17 infiltration.
Conclusion: These results indicate that HFD-induced obesity may exacerbate allergic airway inflammation by mechanisms involving ILC2 and ILC3.
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