Community-level polycyclic aromatic hydrocarbon exposure and circulating microRNAs: Exploring their origins and regulatory functions in immune cells

Potential health impacts of community-level polycyclic aromatic hydrocarbons (PAHs) are closely relevant to the general population, yet their effects on circulating miRNAs are not fully understood. We aimed to profile PAH-associated circulating miRNAs and explore their potential origins and biological functions in immune cells. In a cohort of 160 healthy adults, we identified 81 plasma miRNAs associated with hydroxylated-PAHs (OH-PAHs), predominantly 2-hydroxyfluorene (2-OH-Flu) and 9-hydroxyphenanthrene (9-OH-Phe). Notably, 25 miRNAs showed high specificity in key PAH-target organs, such as brain and liver. In a separate cohort of 16 healthy participants, through immune cell sorting and miRNA sequencing in eight cell subtypes, 19 plasma miRNAs were linked to their levels in different immune cell subtypes. Notably, 2-OH-Flu and 9-OH-Phe may promote CD4⁺ T cells to release miR-222-3p, a carcinogenic and immunoregulatory miRNA, into the bloodstream. We also identified four leukocyte miRNAs associated with OH-PAHs with varying cell enrichment and functions. Among these, 9-OH-Phe was positively and inversely associated with miR-193a-5p in plasma and leukocytes, respectively—with plasma miR-193a-5p mainly derived from neutrophils and participating in DNA damage response. Our study revealed potential toxic mechanisms at the subclinical stage, particularly in immune cells, providing novel insights for the prevention of PAH-related diseases.