Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy.
Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy.
复制标题
DOI：
10.3389/fimmu.2020.599083
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Shamji MH
中科院分区：
文献类型：
--
作者：
Kirtland ME;Tsitoura DC;Durham SR;Shamji MH
toll样受体（TLRs）是先天免疫的重要组成部分，对入侵的病原体提供防御性炎症反应。tlr位于细胞的质膜和胞内体内，可以检测细菌、病毒和真菌的一系列病原体相关分子模式。树突状细胞上的TLR激活可以传播到适应性免疫反应，使它们成为开发预防性和治疗性疫苗的有吸引力的目标。与铝盐等传统佐剂相比，TLR激动剂具有明确的免疫调节特性，有利于抗过敏性T淋巴细胞反应。因此，在变应性鼻炎和哮喘的过敏原免疫治疗（AIT）中，TLRs作为佐剂的潜在应用仍然是一个很大的兴趣。变应性鼻炎是一种由th2驱动、ige介导的疾病，发生在特应性个体中，是对暴露于其他无害的空气过敏原（如花粉、屋尘螨和动物皮屑）的反应。AIT适用于抗组胺药和鼻皮质类固醇不能充分控制症状的变应性鼻炎患者。与抗过敏药物不同，AIT具有疾病改善作用，并可能通过以下机制诱导长期疾病缓解：IgG和IgG4抗体上调，诱导调节性T和B细胞，以及有利于Th1反应的免疫偏差，而Th1反应在停药后仍能维持。然而，这个过程需要长达三年的时间，这突出了对更快起效的更有效治疗的需求。针对不同tlr治疗过敏的激动剂处于不同的发展阶段。合成的TLR4和TLR9激动剂已进入临床试验阶段，而TLR2、TLR5和TLR7激动剂在人体体外实验和动物体内实验中均显示出较强的抗过敏作用。tlr的抗过敏特性主要表现为增强Th1偏差、调节反应和诱导阻断抗体的结合。虽然有希望，但在更大规模的临床试验中还没有观察到持久的效果，在考虑将TLR佐剂纳入AIT之前，还需要进一步的长期研究和与传统AIT的比较试验。在这里，我们批判性地评估了研究tlr的实验和临床研究，并讨论了它们在未来AIT中的潜在作用。
Toll-like receptors (TLRs) are essential components of innate immunity and provide defensive inflammatory responses to invading pathogens. Located within the plasma membranes of cells and also intracellular endosomes, TLRs can detect a range of pathogen associated molecular patterns from bacteria, viruses and fungi. TLR activation on dendritic cells can propagate to an adaptive immune response, making them attractive targets for the development of both prophylactic and therapeutic vaccines. In contrast to conventional adjuvants such as aluminium salts, TLR agonists have a clear immunomodulatory profile that favours anti-allergic T lymphocyte responses. Consequently, the potential use of TLRs as adjuvants in Allergen Immunotherapy (AIT) for allergic rhinitis and asthma remains of great interest. Allergic Rhinitis is a Th2-driven, IgE-mediated disease that occurs in atopic individuals in response to exposure to otherwise harmless aeroallergens such as pollens, house dust mite and animal dander. AIT is indicated in subjects with allergic rhinitis whose symptoms are inadequately controlled by antihistamines and nasal corticosteroids. Unlike anti-allergic drugs, AIT is disease-modifying and may induce long-term disease remission through mechanisms involving upregulation of IgG and IgG4 antibodies, induction of regulatory T and B cells, and immune deviation in favour of Th1 responses that are maintained after treatment discontinuation. This process takes up to three years however, highlighting an unmet need for a more efficacious therapy with faster onset. Agonists targeting different TLRs to treat allergy are at different stages of development. Synthetic TLR4, and TLR9 agonists have progressed to clinical trials, while TLR2, TLR5 and TLR7 agonists been shown to have potent anti-allergic effects in human in vitro experiments and in vivo in animal studies. The anti-allergic properties of TLRs are broadly characterised by a combination of enhanced Th1 deviation, regulatory responses, and induction of blocking antibodies. While promising, a durable effect in larger clinical trials is yet to be observed and further long-term studies and comparative trials with conventional AIT are required before TLR adjuvants can be considered for inclusion in AIT. Here we critically evaluate experimental and clinical studies investigating TLRs and discuss their potential role in the future of AIT.
登录
查看更多内容
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
14.2
作者：
Beeh, Kai-Michael;Kanniess, Frank;Renner, Wolfgang A.
通讯作者：
Renner, Wolfgang A.
影响因子：
6.1
作者：
Berghöfer, B;Frommer, T;Hackstein, H
通讯作者：
Hackstein, H
影响因子：
4.1
作者：
Delaney S;Biffen M;Maltby J;Bell J;Asimus S;Aggarwal A;Kraan M;Keeling D
通讯作者：
Keeling D
影响因子：
14.2
作者：
Brugnolo, F;Sampognaro, S;Parronchi, P
通讯作者：
Parronchi, P