Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma.
Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma.
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DOI：
10.1016/j.jaci.2009.02.009
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发表时间：
2009-04
影响因子：
14.2
通讯作者：
Alam, Rafeul
中科院分区：
文献类型：
--
作者：
Goplen, Nicholas;Karim, Zunayet;Liang, Qiaoling;Gorska, Magdalena M.;Rozario, Sadee;Guo, Lei;Alam, Rafeul
现有的哮喘模型在长期暴露于相同的过敏原时会产生耐受性。建立一个慢性模型，在停止接触过敏原后很长时间内仍能维持哮喘特征。我们对小鼠进行免疫接种，并将小鼠鼻内暴露于单一、双重或三重过敏原（尘螨、豚草和曲霉）的组合中，为期 8 周。接触过敏原三周后，研究了气道高反应性和哮喘的形态学特征。研究了过敏原对树突状细胞的信号作用。致敏和反复接触单一过敏原会引起耐受。对双重、特别是三重过敏原的敏感性突破了耐受性，并建立了 AHR、嗜酸性炎症、肥大细胞和平滑肌增生、粘液产生和气道重塑，这些现象在接触过敏原后至少持续 3 周。在没有佐剂的情况下，粘膜暴露于三重过敏原足以诱发慢性气道炎症。抗IL5和IL13抗体抑制急性哮喘模型中的炎症和AHR，但不能抑制慢性三重过敏原模型。多种过敏原在 p38 MAPK 信号传导和树突状细胞的成熟中产生协同作用，从而以单一过敏原无法达到的水平提供增强的 T 细胞共刺激。对多种过敏原的敏感性导致小鼠慢性哮喘。多种过敏原在树突细胞信号传导和 T 细胞刺激中协同作用，从而避免单一过敏原相关的耐受性发展。我们开发了一种慢性哮喘模型，可以研究和治疗哮喘的长期特征，从而无需进行急性从头过敏原挑战。
Existing asthma models develop tolerance when chronically exposed to the same allergen. To establish a chronic model that sustains features of asthma long after discontinuation of allergen exposure. We immunized and exposed mice to a combination of single, double or triple allergens (dust-mite, ragweed, and Aspergillus) intranasally for 8 weeks. Airway hyperreactivity and morphological features of asthma were studied 3 weeks after the allergen exposure. Signaling effects of the allergens were studied on dendritic cells. Sensitization and repeated exposure to a single allergen induced tolerance. Sensitization to double, and especially triple allergens broke through tolerance and established AHR, eosinophilic inflammation, mast cell and smooth muscle hyperplasia, mucus production and airway remodeling that persisted at least 3 weeks after allergen exposure. Mucosal exposure to triple allergens in the absence of an adjuvant was sufficient to induce chronic airway inflammation. Anti-IL5 and -IL13 antibodies inhibited inflammation and AHR in the acute asthma model but not in the chronic triple allergen model. Multiple allergens produce a synergy in p38 MAPK signaling and maturation of dendritic cells, which provides a heightened T cell co-stimulation at a level that cannot be achieved with a single allergen. Sensitivity to multiple allergens leads to chronic asthma in mice. Multiple allergens synergize in dendritic cell signaling and T cell stimulation that allows escape from the single allergen-associated tolerance development. We have developed a model of chronic asthma that allows for the study and treatment of long-lasting features of asthma obviating the need for acute de novo allergen challenges.
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影响因子：
6.1
作者：
Masuda, T;Tanaka, H;Nagai, H
通讯作者：
Nagai, H
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
影响因子：
2.8
作者：
Sarpong, SB;Zhang, LY;Kleeberger, SR
通讯作者：
Kleeberger, SR
影响因子：
4.4
作者：
Lamhamedi-Cherradi, Salah-Eddine;Martin, Rachel Elizabeth;Moyle, Matthew
通讯作者：
Moyle, Matthew