Université Paris Descartes, Hôpital Necker, Paris, France.
Eur J Immunol. 2011 Jul;41(7):1992-9. doi: 10.1002/eji.201040914. Epub 2011 Jun 6.
The evolution of allergic asthma is tightly controlled by effector and regulatory cells, as well as cytokines such as IL-10 and/or TGF-β, and it is widely acknowledged that environmental exposure to allergens and infectious agents can influence these processes. In this context, the recognition of pathogen-associated motifs, which trigger TLR activation pathways, plays a critical role with important consequences for disease progression and outcome. We addressed the question whether the TLR7 ligand resiquimod (R848), which has been shown to be protective in several experimental allergic asthma protocols, can also suppress typical asthma symptoms once the disease is established. To this end, we used an OVA-induced experimental model of murine allergic asthma in which R848 was injected after a series of challenges with aerosolized OVA. We found that the treatment attenuated allergic symptoms through a mechanism that required Tregs, as assessed by the expansion of this population in the lungs of mice having received R848, and the loss of R848-mediated suppression of allergic responses after in vivo Treg depletion. IL-10 provided only a minor contribution to this suppressive effect that was largely mediated through a TGF-β-dependent pathway, a finding that opens new therapeutic opportunities for the pharmacological targeting of Tregs.
变应性哮喘的发生发展受到效应细胞和调节性细胞以及细胞因子（如 IL-10 和/或 TGF-β）的严密调控，人们普遍认为变应原和感染因子的环境暴露可以影响这些过程。在这种情况下，识别病原体相关模式（触发 TLR 激活途径）起着至关重要的作用，对疾病的进展和结果有着重要的影响。我们提出了一个问题，即已被证明在几种变应性哮喘实验方案中具有保护作用的 TLR7 配体瑞喹莫德（R848）是否可以在疾病确立后抑制典型的哮喘症状。为此，我们使用了一种 OVA 诱导的实验性变应性哮喘小鼠模型，其中在一系列雾化 OVA 挑战后注射 R848。我们发现，这种治疗通过一种需要 Tregs 的机制减轻了过敏症状，这可以通过在接受 R848 的小鼠肺部中该细胞群的扩张来评估，并且在体内 Treg 耗竭后，R848 介导的对过敏反应的抑制作用丧失。IL-10 仅对这种抑制作用有较小的贡献，而这种抑制作用主要是通过 TGF-β 依赖途径介导的，这一发现为 Treg 的药理学靶向提供了新的治疗机会。
