Innate immune cell contribution in wood smoke induced effects to pulmonary function

天然免疫细胞在木材烟雾致肺功能损害中的作用 野火是一个日益严重的全球性问题，也是公众健康的一个重大问题。每年，野火都在继续， 成为头条新闻，因为世界各地发生了数万起火灾，数百万英亩的土地被烧毁。由于影响， 随着气候变化，这些野火变得更加激烈，燃烧时间更长。尽管野火威胁着 野火烟雾影响着我们所有人，特别是随着野火的强度和持续时间的升级， 在全球令人兴奋的新的初步数据显示，来自一个社区的个人淹没了危险的 49天的野火烟雾水平（每日平均：220.9微克/立方米的PM2.5）显示出显著下降， 野火事件后至少两年的肺功能，在老年人（>65岁）中观察到更大的影响 一小部分人此外，我们还证实了肺部炎症和气道高反应性， 在我们的急性木材烟雾暴露的小鼠模型中，细胞因子介导物促进。的目的 这项研究的目的是确定野火烟雾如何影响先天免疫、巨噬细胞亚群和 先天性淋巴样细胞，产生alarmin和炎症介质，导致组织重塑， 肺功能下降。我们提出了中心假设，即ILC 2活性是由IL-33启动的 和巨噬细胞对木材烟雾暴露的反应，导致产生和释放 引发病理学的炎症介质。为了有效地检验这一假设，以下具体 目标1：暴露于WS将导致时间、剂量、年龄和性别依赖性不良反应。 肺部影响目的2：暴露于高水平的野火烟雾将导致先天免疫功能的改变 促进肺部组织重塑的成分。拟议的研究将利用国家的- 蒙大拿大学的吸入和肺生理学核心设施，以开发小鼠模型 社区曝光率。 影响 总之，拟议的尖端小鼠研究补充了正在进行的独特的纵向人类 研究将对野火烟雾引起的健康影响和巨噬细胞产生持续和强大的影响。 免疫生物学该项目的成功完成将提供一个重要的缺失环节成一部小说 环境对呼吸系统健康产生不利影响的机制，并提供了与其他 环境污染物（如香烟烟雾、柴油机废气、颗粒物）可能是 肺功能减弱最后通过了解巨噬细胞亚群如何影响炎症反应 在ILC 2中，治疗方法可以更精确和更有效地开发，从而显著地 为这一日益增长的公共卫生问题提供治疗选择。

Innate immune cell contribution in wood smoke induced effects to pulmonary function Wildfires are a growing global issue, and a significant concern for public health. Each year, wildfires continue to make headlines as tens of thousands of fires and millions of acres burn around the world. Due to the effects of climate change, these wildfires have become more intense and longer burning. Although wildfires threaten lives directly, and wildfire smoke affects us all—particularly as the intensity and duration of wildfires escalates globally. exciting new preliminary data shows that individuals from a community inundated with hazardous levels of wildfire smoke (daily average: 220.9 µg/m3 of PM2.5) for 49 days exhibited a significant decrease in lung function at least two years after the wildfire event, with a greater effect observed in the older (>65 years) fraction of the cohort. Moreover, we demonstrate pulmonary inflammation and airway hyperreactivity, facilitated by cytokine mediators in our mouse model of acute wood smoke exposure. The objective of this proposal is to determine how wildfire smoke affects components of innate immunity, macrophage subsets and innate lymphoid cells, into generating alarmins and inflammatory mediators that result in tissue remodeling and decreased lung function. We propose the central hypothesis that ILC2 activities are initiated by IL-33 and macrophages in response to wood smoke exposure, resulting in the production and release of inflammatory mediators which trigger pathology. To effectively test this hypothesis, the following specific aims will be addressed: Aim 1: Exposure to WS will result in time-, dose-, age-, and sex-dependent adverse pulmonary effects. Aim 2: Exposure to high levels of wildfire smoke will result in alterations to innate immune components that will promote tissue remodeling in the lungs. The proposed studies will utilize the state-of-the- art Inhalation and Pulmonary Physiology Core facility at the University of Montana to develop a mouse model of the community exposures. Impact Together, the proposed cutting-edge murine studies complementing the ongoing unique longitudinal human studies will have a sustained and powerful impact on wildfire smoke-induced health effects and macrophage immunobiology. The successful completion of the project will provide a significant missing link into a novel mechanism by which the environment adversely affects respiratory health, and also provide a link to how other environmental pollutants (e.g. cigarette smoke, diesel exhaust, particulate matter) may serve as risk factors for diminished lung function. Lastly by understanding how macrophage subsets influence inflammatory responses in ILC2s, therapeutic approaches can be developed with greater precision and efficacy, thereby significantly advancing treatment options for this growing public health concern.