Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens
Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens
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DOI：
10.1016/j.alit.2015.04.005
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发表时间：
2015-09-01
影响因子：
6.8
通讯作者：
Asano, Koichiro
中科院分区：
文献类型：
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作者：
Ogawa, Rika;Suzuki, Yusuke;Asano, Koichiro
背景：白细胞介素（IL）-23在哮喘病理生理中的作用仍有争议。我们研究了它在过敏性气道炎症中的作用，在两个不同的抗原使用IL-23-缺陷mice.Methods：过敏性气道炎症进行了评估野生型和IL-23 p19（-/-）小鼠。小鼠腹腔注射卵清蛋白（OVA）或屋尘螨（HDM）致敏，然后将其气道暴露于相同的抗原。采用酶联免疫吸附试验和/或定量聚合酶链反应检测血清中抗原特异性免疫球蛋白水平以及支气管肺泡灌洗液、腹腔灌洗液和肺组织中细胞因子水平。结果：IL-23 p19缺乏导致OVA处理小鼠支气管肺泡灌洗液（BALF）中嗜酸性粒细胞和Th 2细胞因子减少，而HDM处理小鼠BALF中嗜酸性粒细胞增加。腹腔注射OVA与明矾，但不HDM，诱导局部合成IL-6，IL-10和IL-23。抗原特异性IgG（1）的系统性产生部分依赖于IL-23。与此相反，气道暴露于HDM，而不是OVA，诱导IL-23 p19 mRNA在肺中的表达。在IL-23 p19缺陷的小鼠，HDM暴露的肺没有表现出诱导的IL-17 A，负调节嗜酸性inflammation.Conclusions：不同的抗原诱导IL-23在不同部位的身体在我们相似的哮喘模型。在抗原致敏位点的内源性IL-23产生促进2型免疫应答，而IL-23产生和随后的气道中的IL-17 A合成抑制过敏性炎症。Copyright（C）2015，日本变态反应学会. Elsevier B. V.制作和主持。保留所有权利。
Background: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice.Methods: Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction.Results: Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG(1) was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation.Conclusions: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation. Copyright (C) 2015, Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.