Particulate matter PM2.5 is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have shown the association between sustained high level of PM2.5 and the risk of many diseases in the respiratory system, including lung cancer. However, the precise mechanisms through which PM2.5 induces respiratory diseases are still unclear. In this study, we demonstrated that CD4+ and CD8+ T cells following PM2.5 treatment demonstrated significantly elevated mRNA and protein levels of interferon (IFN)-γ, interleukin (IL)-10, IL-17, and IL-21 production. This increase in cytokines required the presence of macrophages, such that CD4+ and CD8+ T cells treated with PM2.5 in the absence of macrophages did not present higher IFN-γ, IL-10, or IL-21 expression. In contrast, PM2.5-treated macrophages could significantly upregulate T cell cytokine secretion, even when excess PM2.5 was removed from cell culture. We also observed a macrophage-dependent upregulation of granzyme A and granzyme B expression by CD4+ and CD8+ T cells following PM2.5 treatment. These PM2.5-stimulated CD4+ and CD8+ T cells potently induced the death of human bronchial epithelial (HBE) cells. Interestingly, the CD4+ and CD8+ T cells presented synergistic effects at inducing HBE cytotoxicity, such that CD4+ T cells and CD8+ T cells combined resulted in higher HBE cell death than the sum of the separate effects of CD4+ T cells and CD8+ T cells. While blocking cytotoxic molecule release significantly compromised the T cell-mediated cytotoxicity against HBE cells, blocking IFN-γ, but not IL-10, could also slightly but significantly reduce T cell-mediated cytotoxicity. Together, these data demonstrated that PM2.5 could promote the inflammation of cytotoxicity of T cells in a macrophage-dependent manner. In addition, PM2.5-treated macrophages presented long-lasting proinflammatory effects on T cells.

译文

:颗粒物PM2.5是一类在许多发展中国家持续高水平飞行的空气颗粒和小滴。流行病学研究表明,持续高水平的PM2.5与呼吸系统多种疾病(包括肺癌)的风险之间存在关联。然而,PM2.5诱发呼吸系统疾病的确切机制仍不清楚。在这项研究中,我们证明了PM2.5治疗后的CD4和CD8 T细胞显示出干扰素(IFN)-γ,白介素(IL)-10,IL-17和IL-21产生的mRNA和蛋白质水平显着提高。细胞因子的这种增加需要巨噬细胞的存在,以致在没有巨噬细胞的情况下用PM2.5处理的CD4和CD8 T细胞不会表现出更高的IFN-γ,IL-10或IL-21表达。相反,即使从细胞培养物中去除了过量的PM2.5,经PM2.5处理的巨噬细胞也可以显着上调T细胞细胞因子的分泌。我们还观察到PM2.5处理后CD4和CD8 T细胞巨噬细胞依赖颗粒酶A和颗粒酶B表达的上调。这些PM2.5刺激的CD4和CD8 T细胞有效诱导人支气管上皮(HBE)细胞死亡。有趣的是,CD4和CD8 T细胞在诱导HBE细胞毒性方面表现出协同作用,因此与CD4 T细胞和CD8 T细胞单独作用的总和相比,CD4 T细胞和CD8 T细胞的结合导致更高的HBE细胞死亡。尽管阻断细胞毒性分子的释放显着损害了针对HBE细胞的T细胞介导的细胞毒性,但阻断IFN-γ(而非IL-10)也可以略微但显着降低T细胞介导的细胞毒性。总之,这些数据表明PM2.5可以以巨噬细胞依赖性方式促进T细胞的细胞毒性炎症。此外,经PM2.5处理的巨噬细胞对T细胞具有持久的促炎作用。

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