Deciphering Allergenic Components Responsible for Differential Sensitization Potentials of Source-Specific Atmospheric Particulate Matter.

Airborne particulate matter (PM) is a major environmental contributor to allergic disease prevalence, yet the skin-sensitizing potency of PM from different emission sources and its active components remain unclear. We adopted the human cell line activation test (h-CLAT) and keratinocyte-dendritic cell (KC-DC) co-culture activation test (COCAT) to evaluate three standard reference materials (SRMs): urban PM (UPM) 1648a, coal fly ash (CFA) 2693, and diesel exhaust particles (DEP) 2975. Distinct source-dependent sensitization profiles were observed. In THP-1 monocultures, 1648a upregulated CD54 expression by stimulating TNF-α and IL-1β secretion. Co-culture with KCs potentiated DC activation against all three SRMs, elevating CD86 and CD54 levels via increased IL-1β and extracellular ATP release. Mechanistically, aryl hydrocarbon receptor (AhR) signaling in HaCaT cells was critical for THP-1 activation. Functional component analysis uncovered that amorphous silica drove 1648a-triggered CD54 upregulation in monocultures, while soot and magnetite, common to all SRMs, along with amorphous and crystalline silica in 1648a, collectively elevated CD86 levels under co-culture. AhR-agonistic soluble components, such as polycyclic aromatic hydrocarbons (PAHs), acted as synergistic regulators. This study presents the first comprehensive evidence that PM of disparate origins induces cutaneous sensitization via differential modulation of KC-DC crosstalk, offering a basis for reducing PM-related allergic risks.