Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma.

Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma.
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IL-33 疫苗可抑制哮喘房尘螨模型中的气道高反应性和炎症。

DOI:
10.1371/journal.pone.0133774
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Nilsson G
Nilsson G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lei Y;Boinapally V;Zoltowska A;Adner M;Hellman L;Nilsson G

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在一些临床和实验研究中发现IL-33及其受体在哮喘和过敏性气道炎症的发展中起重要作用。我们在屋尘螨(HDM)过敏原诱导的气道炎症小鼠模型中评估了接种IL-33疫苗的效果。Balb/c小鼠皮下注射IL-33疫苗,然后鼻内注射HDM长达6周。接种IL-33疫苗可诱导高滴度特异性抗IL-33 IgG抗体,抑制hdm诱导的气道高反应性(AHR)和组织阻尼。疫苗接种还可以减轻hdm引起的支气管肺泡灌洗液(BALF)中嗜酸性粒细胞数量的升高,并抑制气道中炎症细胞的积聚。此外,接种IL-33可降低肺组织匀浆中IL-17A、IL-25、IL-33和TSLP的水平。这些观察结果表明,接种IL-33疫苗可抑制hdm诱导的AHR、气道炎症和炎症细胞因子的产生。结果还表明IL-33在调节远端肺室AHR中起重要作用。因此,施用这种疫苗可能是治疗过敏性哮喘的有效治疗工具。
In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM) allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR) in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma.