Department of Henan Newborn Screening Center, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Public Health, Zhengzhou University, Zhengzhou, China.
Front Immunol. 2019 Apr 24;10:787. doi: 10.3389/fimmu.2019.00787. eCollection 2019.
During silicosis, immune cells, including macrophages, T cells, B cells, and NK cells, participate in fibrosis development through alteration of the immune status. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with a key role in initiating immune responses and sustaining immune tolerance to maintain homeostasis. The relative contribution of DCs to silicosis progression is not well-documented. In the current study, we investigated the phenotypic and functional alterations of peripheral blood mononuclear cell (PBMC)-derived DCs of Sprague-Dawley (SD) rat during immune responses to silica exposure. We established models for direct and indirect exposure of DCs to silica by either treating DCs with silica or coculturing them with alveolar macrophages (AMs) treated with silica, respectively. The functional activity of DCs was analyzed by measuring their expression of costimulatory molecules, fluorescent microparticle uptake, cytokine production, and ability to mediate T cell polarization . , we demonstrated that silica could induce DC migration in response to silica exposure. Our results show that cytokine production by DCs was increased in response to direct silica direct exposure, while indirect silica exposure led to reduced cytokine levels. Moreover, the phagocytic capacity of DCs increased in cocultures after silica exposure. Gene and protein expression analyses showed that silica exposure altered the expression levels of Toll-like receptor pathway proteins and inflammatory factors. DC surface expression of the costimulatory molecules, CD80, CD86, and major histocompatibility complex, was inhibited by exposure to silica, which mediated a Th2-polarizing response . In rats, silica exposure induced migration of DCs from the peripheral blood into the alveoli. These results demonstrate that direct and indirect exposure to silica particles alter the phenotype and function of DCs, thereby regulating immune responses. Such changes may contribute to the development of silicosis by altering DC phenotype, function, and migration and by influencing the balance between Th1 and Th2 cells.
在矽肺中，免疫细胞，包括巨噬细胞、T 细胞、B 细胞和自然杀伤细胞，通过改变免疫状态参与纤维化的发展。树突状细胞（DCs）是具有关键作用的专业抗原呈递细胞（APCs），可启动免疫反应并维持免疫耐受以维持体内平衡。DCs 对矽肺进展的相对贡献尚未得到充分记录。在本研究中，我们研究了矽暴露引起的免疫反应过程中，SD 大鼠外周血单个核细胞（PBMC）衍生的 DC 的表型和功能改变。我们通过用矽处理 DC 或用矽处理的肺泡巨噬细胞（AMs）共培养 DC 分别建立了 DC 直接和间接暴露于矽的模型。通过测量其共刺激分子的表达、荧光微球摄取、细胞因子产生和介导 T 细胞极化的能力来分析 DC 的功能活性。结果表明，矽可以诱导 DC 迁移以响应矽暴露。我们的结果表明，直接暴露于矽时，DC 的细胞因子产生增加，而间接暴露于矽时，细胞因子水平降低。此外，暴露于矽后共培养物中的 DC 吞噬能力增加。基因和蛋白表达分析表明，矽暴露改变了 Toll 样受体途径蛋白和炎症因子的表达水平。矽暴露抑制了 DC 表面共刺激分子 CD80、CD86 和主要组织相容性复合物的表达，介导了 Th2 极化反应。在大鼠中，矽暴露诱导 DC 从外周血迁移到肺泡。这些结果表明，直接和间接暴露于矽颗粒改变了 DC 的表型和功能，从而调节了免疫反应。这些变化可能通过改变 DC 的表型、功能和迁移以及影响 Th1 和 Th2 细胞之间的平衡来促进矽肺的发展。
