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

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 Tcell 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.

Unveiling the potent effect of vitamin D: harnessing Nrf2/HO-1 signaling pathways as molecular targets to alleviate urban particulate matter-induced asthma inflammation

“…Such observations suggest that high HO-1 expression and anti-inflammatory effects may occur during the initial immune phase. This finding is consistent with our previous study showing that the Th1/Th2 ratio remains relatively constant in OVA-induced mice at the same time, Treg/Th17 changes rapidly, eventually leading to pathological lesions in the respiratory tract [ 60 ]. However, to confirm and validate this hypothesis, more relevant experiments need to be conducted.…”

Association between atmospheric concentration of particulate matters and inpatient and outpatient visits for chronic respiratory diseases in Xiamen, China

“…[4] Our previous study suggests the activities of Th17 cells are associated with PM exposure through modulation of interferon regulatory factor 4 and signal transducer and activator of transcription 3 and cause inflammatory responses in the respiratory tracts. [5] Our data suggest negative effects of O 3 exposure on inpatient visit for J40 to J42, J43 to J44, and J47. Such effects are attributed to the fact that most of inpatients are already diagnosed with relevant conditions with very limited outdoor activities, hence less affected by the ambient O 3 levels.…”

“…PM causes acute exacerbation of chronic respiratory diseases by inducing and aggravating airway and lung inflammation [4] . Our previous study suggests the activities of Th17 cells are associated with PM exposure through modulation of interferon regulatory factor 4 and signal transducer and activator of transcription 3 and cause inflammatory responses in the respiratory tracts [5] . Our data suggest negative effects of O 3 exposure on inpatient visit for J40 to J42, J43 to J44, and J47.…”

Inhaled particulate matter affects immune responsiveness of human lung phagocytes to mycobacteria

“…Literature suggests a relationship between PM exposure and T cell functions (25,26), including T cell mediators/activation, not measured here, which may ineffectively prime AM. In addition, PM exposure has been related to variations in pattern recognition receptor expression (27), global effects on T cell recruitment (28), interruption of transcription factor gene expression (29), or differential antibody production of isotype switching (30). Collectively, these studies set the platform for the impact of inhaled PM on antimycobacterial immune cell functions.…”