Benzoapyrene exacerbates bone destruction by inhibiting Treg differentiation, impairing Treg function and promoting osteoclastogenesis in rats with collagen-induced arthritis

Emerging evidence has shown that exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for rheumatoid arthritis (RA). Benzo a pyrene (BaP), a representative PAH congener, exacerbates the development of collagen-induced arthritis (CIA) in animal models. However, the underlying mechanisms, particularly those involving the immune dynamic and functional plasticity of regulatory T cells (Tregs), remain largely unknown. In this study, a rat CIA model was used to evaluate the effect of BaP on RA onset following intervention with the aryl hydrocarbon receptor (AHR) antagonist CH223191. The effects of BaP on the differentiation of regulatory T cells (Tregs) and osteoclasts (OCs) were subsequently assessed. Furthermore, the significance of the BaP–AHR axis in the pathogenesis of RA was determined using reverse transcription polymerase chain reaction (RT PCR), flow cytometry and immunohistochemistry. Finally, the influence of BaP on osteoclastogenesis was confirmed through the coculture of Tregs and bone marrow-derived monocytes (BMMs). Our findings indicate that BaP significantly exacerbates joint inflammation and bone destruction in rats with CIA. Mechanistically, BaP not only suppresses the differentiation of Tregs but also impairs the ability of Tregs to secrete anti-inflammatory cytokines, such as IL-10 and TGF-β. Furthermore, BaP actively promotes the differentiation of OCs. These detrimental effects are predominantly mediated by activation of the AHR signalling pathway. These results reveal the cellular and molecular mechanisms of BaP during RA pathogenesis, providing novel therapeutic targets for RA. • BaP exacerbates bone destruction in collagen-induced arthritis (CIA) rats. • BaP activates AHR to suppress Treg differentiation and immunoregulatory capacity. • BaP promotes OC formation through activation of AHR signalling. • BaP impairs Treg-mediated osteoclastogenesis suppression by modulating Treg plasticity.