Pulmonary, Critical Care, Sleep & Allergy Division; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ann Allergy Asthma Immunol. 2012 Oct;109(4):266-273.e2. doi: 10.1016/j.anai.2012.06.015. Epub 2012 Jul 24.
Organic dust exposure in agricultural environments induces an inflammatory response that attenuates over time, yet repetitive dust exposures result in chronic lung diseases. Animal models resembling this chronic lung inflammatory response have been developed, yet the underlying cellular mechanisms are not well defined.
Because mice repetitively exposed to organic dust extracts (DE) display increased CD3+ T cell lung infiltrates, we sought to determine the phenotype and importance of these cells.
Mice received swine confinement DE repetitively for 3 weeks by established intranasal inhalation protocol. Studies were conducted with peptidoglycan (PGN) because it is a major DE component in large animal farming environments and has shared similar biologic effects with DE. Enumeration of T cells and intracellular cytokine profiles were conducted by flow cytometry techniques. Whole lung homogenate cytokines were analyzed by multiplex immunoassay. T cell receptor (TCR) αβ knockouts were used to determine the functional importance of αβ-expressing T cells.
DE increased lung-associated CD3+CD4+ T cells and interleukin (IL)-17 (but not IL-4, interferon [IFN]-γ, IL-10) producing CD4+ T cells. PGN treatment resulted in increased IL-17 and IFN-γ producing CD4+ T cells and IFN-γ producing CD8+ T cells. Both DE and PGN augmented expression of cytokines associated with Th1 and Th17 polarization in lung homogenates. DE-induced lung mononuclear aggregates and bronchiolar compartment inflammation were significantly reduced in TCR knockout animals; however, neutrophil influx and alveolar compartment inflammation were not affected.
Studies demonstrated that DE and PGN exposure promote a Th1/Th17 lung microenvironment and that αβ-expressing T cells are important in mediating DE-induced lung pathologic conditions.
农业环境中的有机粉尘暴露会引起炎症反应，随着时间的推移炎症反应会减弱，但反复的粉尘暴露会导致慢性肺部疾病。已经开发出了类似这种慢性肺部炎症反应的动物模型，但其中的细胞机制尚不清楚。
由于反复暴露于有机粉尘提取物（DE）的小鼠肺部 CD3+T 细胞浸润增加，我们试图确定这些细胞的表型和重要性。
通过既定的鼻腔内吸入方案，用猪舍 DE 重复对小鼠进行 3 周的重复暴露。由于 PG 是大型动物养殖环境中 DE 的主要成分之一，并且与 DE 具有相似的生物学效应，因此进行了 PG 研究。通过流式细胞术技术对 T 细胞进行计数和细胞内细胞因子谱分析。通过多重免疫测定法分析肺匀浆细胞因子。使用 T 细胞受体（TCR）αβ 敲除小鼠来确定表达 TCRαβ 的 T 细胞的功能重要性。
DE 增加了肺部相关的 CD3+CD4+T 细胞和白细胞介素（IL）-17（但不是 IL-4、干扰素[IFN]-γ、IL-10）产生的 CD4+T 细胞。PG 处理导致 IL-17 和 IFN-γ 产生的 CD4+T 细胞和 IFN-γ 产生的 CD8+T 细胞增加。DE 和 PG 均增加了肺匀浆中与 Th1 和 Th17 极化相关的细胞因子的表达。在 TCR 敲除动物中，DE 诱导的肺单核细胞聚集和细支气管腔炎症明显减少；然而，中性粒细胞浸润和肺泡腔炎症不受影响。
研究表明，DE 和 PG 暴露促进了 Th1/Th17 肺部微环境，并且表达 TCRαβ 的 T 细胞在介导 DE 诱导的肺部病理状况中很重要。
