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Novel Toll-Like Receptor 9 Agonist Derived from Cryptococcus neoformans Attenuates Allergic Inflammation Leading to Asthma Onset in Mice.
International Archives of Allergy and Immunology ( IF 2.5 ) Pub Date : 2020-06-25 , DOI: 10.1159/000508535
Kaori Dobashi-Okuyama 1 , Kazuyoshi Kawakami 2, 3 , Tomomitsu Miyasaka 4 , Ko Sato 3 , Keiko Ishii 2 , Kaori Kawakami 1 , Chiaki Masuda 1 , Syugo Suzuki 2 , Jun Kasamatsu 3 , Hideki Yamamoto 2 , Daiki Tanno 2 , Emi Kanno 5 , Hiromasa Tanno 5 , Tasuku Kawano 1 , Motoaki Takayanagi 1 , Tomoko Takahashi 1 , Isao Ohno 6
Affiliation  

Introduction: The enhanced type 2 helper (Th2) immune response is responsible for the pathogenesis of allergic asthma. To suppress the enhanced Th2 immune response, activation of the Th1 immune response has been an alternative strategy for anti-asthma therapy. In this context, effective Th1-inducing adjuvants that inhibit the development of allergic asthma but do not flare the side effects of the primary agent are required in clinical treatment and preventive medicine. Objective: In this study, we aimed to determine the regulation of the Th2 type immune response in asthma by a novel immunostimulatory oligodeoxynucleotide (ODN) derived from Cryptococcus neoformans, termed ODN112, which contains a cytosine-guanine (CG) sequence but not canonical CpG motifs. Methods: Using an ovalbumin-induced asthma mouse model, we assessed the effect of ODN112 on prototypical asthma-related features in the lung and on the Th1/Th2 profile in the lymph nodes and lung of mice treated with ODN112 during sensitization. Results and Conclusion: ODN112 treatment attenuated asthma features in mice. In the bronchial lymph nodes of the lungs and in the spleen, ODN112 increased interferon-γ production and attenuated Th2 recall responses. In dendritic cells (DCs) after allergen sensitization, ODN112 enhanced cluster of differentiation (CD) 40 and CD80 expression but did not alter CD86 expression. Interleukin-12p40 production from DCs was also increased in a Th2-polarizing condition. Our results suggest that ODN112 is a potential Th1-inducing adjuvant during Th2 cell differentiation in the sensitization phase.
Int Arch Allergy Immunol


中文翻译:

新型隐球菌衍生的新型Toll-like受体9激动剂可减轻过敏性炎症,导致小鼠哮喘发作。

简介:增强的2型辅助(Th2)免疫应答与过敏性哮喘的发病机理有关。为了抑制增强的Th2免疫应答,激活Th1免疫应答已成为抗哮喘治疗的替代策略。在这种情况下,在临床治疗和预防医学中需要有效的诱导Th1的佐剂,该佐剂可抑制过敏性哮喘的发展,但又不散发主药的副作用。目的:在这项研究中,我们旨在确定一种新的隐球菌衍生的新型免疫刺激性寡脱氧核苷酸(ODN)(称为ODN112)对哮喘中Th2型免疫应答的调节作用,该寡核苷酸包含胞嘧啶鸟嘌呤(CG)序列但不包含典型的CpG图案。方法:使用卵清蛋白诱导的哮喘小鼠模型,我们评估了ODN112对在致敏过程中用ODN112处理的小鼠肺部原型哮喘相关特征以及淋巴结和肺中Th1 / Th2谱的影响。结果与结论:ODN112治疗减弱了小鼠的哮喘特征。在肺和脾脏的支气管淋巴结中,ODN112会增加干扰素-γ的产生并减弱Th2的召回反应。在过敏原致敏后的树突状细胞(DC)中,ODN112增强了分化簇(CD)40和CD80的表达,但没有改变CD86的表达。在Th2极化条件下,DC的白介素12p40产量也增加了。我们的结果表明,ODN112是敏化阶段Th2细胞分化过程中潜在的Th1诱导佐剂。
Int Arch过敏免疫
更新日期:2020-06-25
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