Yacoub Mona-Rita, Colombo Giselda, Marcucci Francesco, Caminati Marco, Sensi Laura, Di Cara Giuseppe, Frati Franco, Incorvaia Cristoforo
Allergy and Immunology Unit, San Raffaele Scientific Institute, Milan, Italy.
Inflamm Allergy Drug Targets. 2012 Aug 1;11(4):285-91. doi: 10.2174/187152812800958988.
The most common allergic diseases, and especially the respiratory disorders such as rhinitis and asthma, are closely related to the allergic inflammation elicited by the causative allergen. This makes inflammation the main target of anti-allergic therapies. Among the available treatments, allergen specific immunotherapy (AIT) has a patent effect on allergic inflammation, which persists also after its discontinuation, and is the only therapy able to modify the natural history of allergy. The traditional, subcutaneous route of administration was demonstrated to modify the allergen presentation by dendritic cells (DCs) that in turn correct the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation and characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy of Th2 or to tolerance, the latter being related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual AIT with high allergen doses proved to be similar to subcutaneous immunotherapy. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa, with particular importance for mucosal DCs, plays a crucial role in inducing tolerance to the administered allergen.
最常见的过敏性疾病，尤其是呼吸道疾病，如鼻炎和哮喘，与由致敏变应原引发的过敏性炎症密切相关。这使得炎症成为抗过敏治疗的主要靶点。在现有的治疗方法中，变应原特异性免疫疗法（AIT）对过敏性炎症有显著效果，即使在停药后仍持续存在，并且是唯一能够改变过敏自然病程的疗法。传统的皮下给药途径已被证明可改变树突状细胞（DCs）的变应原呈递，进而纠正变应原特异性T细胞的表型，从过敏性炎症典型的Th2型反应（其特征为产生IL-4、IL-5、IL-13、IL-17和IL-32细胞因子）转变为Th1型反应。这种免疫偏差与IFN-γ和IL-2产生增加以及Th2无能或耐受有关，后者与变应原特异性调节性T（Treg）细胞的产生有关，这些细胞产生如IL-10和TGF-β等细胞因子。高剂量变应原舌下AIT期间观察到的抗炎机制被证明与皮下免疫疗法相似。活检获得的数据清楚地表明，口腔黏膜的病理生理学，对黏膜DCs尤为重要，在诱导对所给变应原的耐受性方面起着关键作用。
