Regulation of T-cell activation in the airway mucosa of rats expressing low versus high IgE responder phenotype

表达低 IgE 反应表型与高 IgE 反应表型的大鼠气道粘膜 T 细胞活化的调节

• 批准号: nhmrc : 458546
• 负责人: Dr Deborah Strickland
• 金额: $ 47.55万
• 依托单位: The University of Western Australia
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-t-cell-responder-phenotype/76263
• 关键词: Regulation; cell; activation; airway; mucosa

We have established an experimental rat model of allergic airways inflammation which mimics human asthma. Interactions occurring between airway mucosal dendritic cells and CD4+ Th2 (effector) cell populations are responsible for the late phase response (LPR) component of asthma exacerbations, including airways hyperresponsiveness (AHR). We have previously demonstrated that termination of the LPR and prevention of its continual recurrence in the face of ongoing aeroallergen challenge is established via the induction of a state of dynamic equilibrium, mediated by local T regulatory cells (Treg) which act to functionally silence local Th2 memory (effector) cells. Maintenance of protective Treg activity is dependent upon continuing allergen exposure as cessation of exposure leads to waning of Treg numbers and function and release of mucosal allergen specific Th2 cells from control. These studies have primarily involved low IgE responder (LR) PVG rats (normals or nonatopics). The present study will focus on elucidating the control of Th2 dependent immune responses to inhaled antigen in high IgE responder (HR) BN rats (atopics). Studying these two strains in parallel enables a comparison between the extremes of the spectrum of susceptibility to both the induction and the expression of Th2 immunity in the airways. A more detailed understanding of the cellular interactions occurring within the airway mucosa and draining lymph nodes and the mechanisms responsible for the maintenance of immunological homeostasis within the airways will provide new insights into the pathogenesis of inflammatory airway diseases such as atopic asthma. This will enable further development and possibly illuminate other avenues of intervention for more effective therapeutic strategies used in the control of asthma, which is the long term goal of this research.

我们建立了一种模拟人类哮喘的大鼠过敏性气道炎症模型。气道粘膜树突状细胞和CD4+ Th2（效应）细胞群之间发生的相互作用是哮喘急性发作的晚期反应（LPR）成分的原因，包括气道高反应性（AHR）。我们以前已经证明，终止LPR和预防其持续复发，面对正在进行的空气过敏原的挑战，是建立通过诱导的动态平衡状态，介导的局部T调节细胞（Treg）的功能沉默当地的Th2记忆（效应）细胞。保护性Treg活性的维持依赖于持续的过敏原暴露，因为暴露的停止导致Treg数量和功能的减弱以及粘膜过敏原特异性Th2细胞从对照中的释放。这些研究主要涉及低IgE应答（LR）PVG大鼠（正常或无特异性）。本研究的重点是阐明高IgE应答（HR）BN大鼠（特应性）吸入抗原的Th2依赖性免疫应答的控制。平行研究这两种菌株能够比较气道中Th2免疫诱导和表达的易感性谱的极端情况。更详细地了解气道粘膜和引流淋巴结内发生的细胞相互作用以及负责维持气道内免疫稳态的机制，将为炎症性气道疾病（如特应性哮喘）的发病机制提供新的见解。这将使进一步的发展，并可能照亮其他途径的干预更有效的治疗策略用于控制哮喘，这是本研究的长期目标。