IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters

Respiratory Research

Jiaxu Hong¹  Xiaoliang Lin²  Jinzhun Wu²  Dandan Ge²  Qiyuan Li²  Chuan Wu³  Zuojia Chen³  Cheng Li⁴  Zuguo Liu⁴  Shuiping Wu⁵  Yulin Zhou⁶  Kuai Liu⁷  Ying Zhou⁷  Lingyun Hou⁷  Taoling Zhong⁷  Chaoying Wang⁸  Hui Qi⁸ 

[1] Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University;Department of Pediatrics, the First Affiliated Hospital of Xiamen University;Experimental Immunology Branch, National Cancer Institute, NIH;Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University;Marine Chemistry and Toxicology Research Center, College of the Environment & Ecology, Xiamen University;Maternal and Child Health Hospital Affiliated Xiamen University;National Institute of Data Science in Health and Medicine, School of Medicine, Xiamen University;The 980st Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA);

关键词: Particulate matters;    Gene expression profiling;    Allergic respiratory disease;    Imbalanced T-cell differentiation;    Transcription factor;   

DOI  :  10.1186/s12931-020-01368-2

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown