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BACKGROUND

Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated.

METHODS

To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM.

RESULTS

We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure.

CONCLUSIONS

Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

背景

已知颗粒物 (PM) 会引起人体的炎症反应。尽管先前的研究已经证实了 PM 在细胞系和动物模型中的免疫原性，但 PM 暴露在呼吸系统中的效应物以及 PM 免疫原性的调节剂尚未完全阐明。

方法

为了鉴定人呼吸系统中 PM 暴露的潜在效应物，并更好地了解 PM 免疫原性的生物学，我们对来自中国北方的 171 名健康受试者的外周血单核细胞进行了基因表达谱分析，以鉴定与 PM 暴露相关的共表达基因模块。我们推断调节共表达的转录因子，并在原代 T 细胞和用 PM 处理的小鼠中验证其与 T 细胞分化的关联。

结果

我们报告了两个转录因子，IRF4 和 STAT3，作为人 PM 暴露反应中基因表达的调节剂。我们证实 PM 对 IRF4 和 STAT3 的激活与小鼠呼吸道中 T 细胞分化失衡强烈相关，且具有时间敏感性。我们还验证了 PM 暴露的后续炎症反应。此外，我们表明，随着 PM 暴露，磷酸化的 IRF4 和 STAT3 蛋白水平增加。