Solitary chemosensory / tuft cells in lung regeneration and inflammation

项目摘要/摘要 呼吸道病毒感染是哮喘发病的主要风险因素。 此外，严重的流感损伤可能会导致无效的修复和持续的损失 肺功能。由病毒引起的肺损伤引起的持久变化 可能解释慢性病的原因还不清楚。我们最近发现了异位簇毛/ 甲型H1N1流感后肺远端出现孤立性化学感觉细胞 感染。由于SCC越来越被认为是两者的关键协调者 炎症和上皮组织再生和重塑，我们假设它们是一种 可能是慢性肺部病变的驱动因素。这项提案将针对中央 假设异位SCCs的灭活/消融将促进解决 减少慢性Th2偏向炎症性疾病， 但也可能增加对Th2反应控制的病原体的易感性 在感染流感之后。解决这一假设的主要目标是1) 确定鳞癌的存在和特定的鳞状细胞癌衍生信号对上皮细胞的影响 祖细胞(命运和增殖)在修复过程中，和2)决定是否 鳞状细胞的发展影响Th2介导的炎症性疾病(哮喘)或 寄生保护。该项目的完成将验证SCC作为重要的驱动因素 肺部疾病，还将有助于识别特定的SCC效应因子 可以在减弱的同时保留寄主保护益处的途径 他们对病理学的贡献。

Project Summary / Abstract Respiratory viral infections represent a major risk factor for the development of asthma. Moreover, severe influenza injury can result in ineffective repair and persistent loss of pulmonary function. The enduring changes caused by viral-induced lung injury that might explain chronic disease are not understood. We recently identified ectopic tuft / solitary chemosensory cells (SCCs) arising in the distal lung after H1N1 influenza infection. Since SCCs are increasingly recognized as critical orchestrators of both inflammation and epithelial tissue regeneration and remodeling, we posit that they are a likely driver of chronic lung pathology. This proposal will address the central hypothesis that inactivation / ablation of ectopic SCCs will promote the resolution of dysplastic remodeling and reduce chronic Th2-biased inflammatory disease, but may also increase susceptibility to pathogens controlled by Th2 responses following influenza infection. The major aims to address this hypothesis are to 1) ascertain the effects of SCC presence and specific SCC-derived signals on epithelial progenitor cells (fate and proliferation) during repair, and 2) determine whether the development of SCCs impacts Th2-mediated inflammatory disease (asthma) or parasitic protection. Completion of this project will validate SCCs as important drivers of pulmonary disease and will also facilitate identification of specific SCC effector pathways that could allow for preservation of host-protective benefits while attenuating their contribution to pathology.