Dean Logan S, Wahl Maëlis, Threatt Alissa N, Pauly Morgan, Barahona Melea, Oyewole Emmanuel O, Nordgren Tara M
Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO, USA.
Department of Environmental and Radiological Health Sciences, Colorado State University State University, Fort Collins, CO, USA.
Lipids Health Dis. 2025 Jul 2;24(1):227. doi: 10.1186/s12944-025-02651-1.
Exposure of the lungs to particulate matter (i.e. dust, wildfire smoke, air pollution) places individuals at an increased risk for developing chronic respiratory disease. Recent work has demonstrated the efficacy of omega-3 fatty acids and their metabolites in promoting the resolution of prolonged inflammation, however a comprehensive understanding of how omega-3 fatty acid balance impacts immune cell populations and crosstalk remains undescribed. We developed a 17-marker, 14-color spectral flow cytometry method to characterize the immunophenotypic changes in the bronchoalveolar space and lung tissue following 14 days of repetitive organic dust exposure or PBS vehicle. The populations of immune cells were compared in C57BL/6 (WT) and a transgenic model of increased omega-3 fatty acid (Fat-1) mice. Histopathologic examination revealed no difference between WT and Fat-1 mice at baseline or following organic dust exposure. Immune cell makeup within the bronchoalveolar space and lung tissue differed between WT and Fat-1 mice, with and without organic dust exposure. Fat-1 mice demonstrated a monocyte-dominant response compared to WT in both the airway and the lung tissue. Intriguingly, this monocyte-dominance was more prominent in female Fat-1 mice in the lung tissue and male Fat-1 mice in the airway. This suggests that monocyte populations are preferentially loaded following organic dust exposure in the lung and airways as a result omega-3 fatty acid metabolite-linked resolution processes, and that sex-dependent factors in this immune response are pivotal to consider in therapeutic strategies aimed at mitigating disease.
肺部暴露于颗粒物（如灰尘、野火烟雾、空气污染）会使个体患慢性呼吸道疾病的风险增加。最近的研究表明，ω-3脂肪酸及其代谢产物在促进长期炎症消退方面具有功效，然而，对于ω-3脂肪酸平衡如何影响免疫细胞群体和细胞间相互作用的全面理解仍未得到描述。我们开发了一种17标记、14色光谱流式细胞术方法，以表征在重复暴露于有机粉尘或PBS载体14天后支气管肺泡腔和肺组织中的免疫表型变化。在C57BL/6（野生型）小鼠和ω-3脂肪酸增加的转基因模型（Fat-1）小鼠中比较了免疫细胞群体。组织病理学检查显示，野生型和Fat-1小鼠在基线时或有机粉尘暴露后没有差异。在有无有机粉尘暴露的情况下，野生型和Fat-1小鼠的支气管肺泡腔和肺组织中的免疫细胞组成有所不同。与野生型相比，Fat-1小鼠在气道和肺组织中均表现出以单核细胞为主的反应。有趣的是，这种单核细胞优势在肺组织中的雌性Fat-1小鼠和气道中的雄性Fat-1小鼠中更为明显。这表明，由于ω-3脂肪酸代谢产物相关的消退过程，单核细胞群体在肺部和气道有机粉尘暴露后优先聚集，并且在旨在减轻疾病的治疗策略中，这种免疫反应中的性别依赖性因素是需要考虑的关键因素。
