Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma.
Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma.
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使用含有 Ag85A-Mtb32 的腺病毒载体结核疫苗进行免疫可有效缓解过敏性哮喘。
DOI：
10.1007/s00109-017-1614-5
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Zhang Y;Feng Y;Li L;Ye X;Wang J;Wang Q;Li P;Li N;Zheng X;Gao X;Li C;Li F;Sun B;Lai K;Su Z;Zhong N;Chen L;Feng L
摘要：目前过敏性哮喘的治疗主要是改善症状而不是抑制疾病进展。调节过度的 2 型辅助 T (Th2) 反应可能会预防哮喘恶化。在这项研究中，我们研究了 Ad5-gsgAM（一种携带两种分枝杆菌抗原 Ag85A 和 Mtb32 的腺病毒载体）对过敏性哮喘的保护作用。使用卵清蛋白 (OVA) 诱导的哮喘小鼠模型，我们发现 Ad5-gsgAM 比卡介苗 (BCG) 诱导更多的 Th1 偏向 CD4+T 和 CD8+T 细胞。 OVA 攻击后，与使用或不使用 BCG 免疫的小鼠相比，Ad5-gsgAM 免疫的小鼠表现出显着降低的气道炎症。总血清免疫球蛋白 E 和肺诱导型一氧化氮合酶均有效降低。支气管肺泡灌洗液 (BALF) 中的细胞因子谱也受到调节，干扰素-γ (IFN-γ) 水平升高以及白细胞介素 (IL)-4、IL-5 和 IL-13 水平降低证明了这一点。抗炎细胞因子IL-10急剧增加，而促炎细胞因子IL-33显着减少。重要的是，外源性 IL-33 消除了 Ad5-gsgAM 的保护作用，表明对 IL-33/ST2 轴的抑制在很大程度上有助于预防过敏性炎症。此外，调节性 T 细胞对于调节异常 Th2 反应以及 IL-33/ST2 轴至关重要。这些结果表明，通过腺病毒载体分枝杆菌抗原疫苗接种调节 IL-33/ST2 轴可能为过敏性炎症气道疾病提供临床益处。关键信息•Ad5-gsgAM 在小鼠中引发 Th1 反应并抑制 Th2 介导的过敏性哮喘。•Ad5-gsgAM 通过减少 IL-33 分泌而不是 ILC2 募集来抑制 IL-33/ST2 轴。•Treg 对于调节 Th2 反应和抑制 Th2 介导的过敏性哮喘至关重要。 Ad5-gsgAM 的 IL-33/ST2 轴。
AbstractCurrent treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. Regulating the excessive T helper type 2 (Th2) responses may prevent asthma exacerbation. In this study, we investigated the protective effects of Ad5-gsgAM, an adenovirus vector carrying two mycobacterial antigens Ag85A and Mtb32, against allergic asthma. Using an ovalbumin (OVA)-induced asthmatic mouse model, we found that Ad5-gsgAM elicited much more Th1-biased CD4+T and CD8+T cells than bacillus Calmette-Guérin (BCG). After OVA challenge, Ad5-gsgAM-immunized mice showed significantly lowered airway inflammation in comparison with mice immunized with or without BCG. Total serum immunoglobulin E and pulmonary inducible-nitric-oxide-synthase were efficiently reduced. The cytokine profiles in bronchial-alveolar-lavage-fluids (BALFs) were also modulated, as evidenced by the increased level of interferon-γ (IFN-γ) and the decreased level of interleukin (IL)-4, IL-5, and IL-13. Anti-inflammatory cytokine IL-10 was sharply increased, whereas pro-inflammatory cytokine IL-33 was significantly decreased. Importantly, exogenous IL-33 abrogated the protective effects of Ad5-gsgAM, revealing that the suppression of IL-33/ST2 axis substantially contributed to protection against allergic inflammation. Moreover, regulatory T cells were essential for regulating aberrant Th2 responses as well as IL-33/ST2 axis. These results suggested that modulating the IL-33/ST2 axis via adenovirus-vectored mycobacterial antigen vaccination may provide clinical benefits in allergic inflammatory airways disease.Key messages•Ad5-gsgAM elicits Th1 responses and suppresses Th2-mediated allergic asthma in mice.•Ad5-gsgAM inhibits IL-33/ST2 axis by reducing IL-33 secretion but not ILC2 recruiting.•Treg is essential for modulating Th2 responses and IL-33/ST2 axis by Ad5-gsgAM.
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DOI：
10.4049/jimmunol.1100436
发表时间：
2011-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mitchell C;Provost K;Niu N;Homer R;Cohn L
通讯作者：
Cohn L
影响因子：
5.8
作者：
Bosnjak B;Stelzmueller B;Erb KJ;Epstein MM
通讯作者：
Epstein MM
DOI：
10.4168/aair.2014.6.3.201
发表时间：
2014-05
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Kim YJ;Kim HJ;Kang MJ;Yu HS;Seo JH;Kim HY;Park SJ;Lee YC;Hong SJ
通讯作者：
Hong SJ
影响因子：
5.6
作者：
Jin, Rong;Guo, Sheng;Zhang, Jian-hua
通讯作者：
Zhang, Jian-hua
DOI：
10.4049/jimmunol.0904214
发表时间：
2010-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Naura AS;Zerfaoui M;Kim H;Abd Elmageed ZY;Rodriguez PC;Hans CP;Ju J;Errami Y;Park J;Ochoa AC;Boulares AH
通讯作者：
Boulares AH