Acute arsenic exposure induces CD4 T cell subpopulations differentiation in spleen and thymus with the involvement of DAMPs-TLR4/NF-κB signaling pathway.

Growing evidence indicates that exposure to arsenic could be linked to immune-related issues. Nevertheless, the relevant molecular mechanisms are not well understood. To explore the impacts of acute exposure to sodium arsenite (NaAsO) on transcription factors and cytokines related to the differentiation of CD4 T cell subsets in mice immune organs, as well as the potential mechanism underlying the arsenic immunotoxicity. Female C57BL/6 mice received intragastric exposure to NaAsO at doses of 2.5, 5, and 10 mg/kg for a duration of 24 h to observe the changes in inflammatory reactions, CD4 T cell differentiation, and TLR-DAMP interactions using the assayed method of flow cytometry, ELISA, real-time PCR, and western blot. Arsenic markedly reduced the weights and indices of the spleen and thymus, and flow cytometry revealed that arsenic decreased the relative frequency of CD4 T cell subpopulation and the ratios of CD4/CD8 in spleen. Arsenic up-regulated serum pro-inflammatory cytokine levels of tumor necrosis factor α (TNF-α), IL-1β, and IL-6, as well as mRNA levels of TNF-α, IL-1β, and IL-6 within the spleen and thymus. Additionally, the expression of T helper 1 (Th1), Th2, and regulatory T cell (Treg) related transcription factors and cytokines was markedly increased in arsenic-treated mice, whereas the expression of Th17-related transcription factors and cytokines were markedly decreased in arsenic-treated mice when in comparison to the group of control. Moreover, arsenic remarkably elevated the expression of proteins that participated within the DAMPs-TLR4/NF-κB signaling pathway including TLR4, MD2, MyD88, and NF-κB. Acute arsenic exposure-induced variation of inflammatory reactions and CD4 T cell subsets differentiation is probably correlated with activation of the DAMPs-TLR4/NF-κB signaling pathway.