Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like symptoms in mice.

Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like symptoms in mice.
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鼻质花粉敏化诱导小鼠局部 - 过敏性 - rhinitis症状。

DOI:
10.1371/journal.pone.0103540
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Yoshimoto T
Yoshimoto T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kato Y;Akasaki S;Muto-Haenuki Y;Fujieda S;Matsushita K;Yoshimoto T

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近年来,人们提出了局部变应性鼻炎(LAR)的概念,即局部产生IgE,血清抗原特异性IgE阴性的鼻炎症状。然而,LAR的自然发展过程和疾病的发病机制尚不清楚。这项研究调查了变应性鼻炎小鼠的病理生理学,最初通过鼻腔途径用豚草花粉致敏。连续几天给小鼠鼻腔注射豚草花粉,而不事先系统免疫过敏原。豚草花粉经鼻腔连续致敏后,第7天时变应原特异性增加,出现打喷嚏、嗜酸性粒细胞渗入和局部IgE的产生,但未检测到血清抗原特异性IgE。Th2细胞早在第3天就在鼻和颈淋巴结内聚集,这些症状是人类LAR的特征。豚草花粉持续鼻腔暴露3周可导致典型变应性鼻炎的发作,并伴有全身特应性反应,当过敏原注入肺内时,对肺部炎症有不利影响。Fcer1a−/−小鼠打喷嚏有缺陷,但嗜酸性粒细胞浸润正常。相反,RAG2−/−小鼠在打喷嚏和嗜酸性粒细胞渗透方面都存在缺陷,这表明T细胞在该病的发病机制中发挥着核心作用。这些观察表明,对非特应性个体的鼻变应原致敏可以诱导LAR。由于局部Th2细胞积聚是LAR的首发症状,而Th2细胞在疾病中起核心作用,以T细胞为基础的方法可能有助于LAR的诊断和治疗。
Recently, the concept of local allergic rhinitis (LAR) was established, namely rhinitis symptoms with local IgE production and negative serum antigen-specific IgE. However, the natural course of LAR development and the disease pathogenesis is poorly understood. This study investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route. Mice were nasally administrated ragweed pollen over consecutive days without prior systemic immunization of the allergen. Serial nasal sensitization of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic infiltration, and the production of local IgE by day 7, but serum antigen-specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph nodes as early as day 3. These symptoms are characteristic of human LAR. Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of classical AR with systemic atopy and adversely affected lung inflammation when the allergen was instilled into the lung. Fcer1a −/− mice were defective in sneezing but developed normal eosinophilic infiltration. Contrary, Rag2 −/− mice were defective in both sneezing and eosinophilic infiltration, suggesting that T cells play a central role in the pathogenesis of the disease. These observations demonstrate nasal allergen sensitization to non-atopic individuals can induce LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a central role in the disease, a T-cell-based approach may aid the diagnosis and treatment of LAR.
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