Radon (222Rn) is a naturally occurring radioactive gas, ionizing radiation emitted by the radon induces oxidative stress and the up-regulation of inflammatory proteins, which may cause lung damage or cancer. However, the underlying pathogenesis remains to be determined. effector T helper cells are key in mediating the host's protection and immune homeostasis. In this study we revealed that, accompanied by the activation of effector T helper cells, there is a significant increase in C-C motif chemokine ligand 5 (Ccl5) in the lung of mice after cumulative inhalation of radon at 3, 9, 21, 45, 90, and 180 working level months (WLM). In vitro experiments showed that Ccl5 attracts DC migration and promotes the activation of effector T helper cells in the Ccl5-DC and T cells co-culture model. Of particular interest, Ccl5 neutralization in vivo inhibited the migration of DC cells and the subsequent activation of effector T helper cells, which finally protected mice from radon-induced lung damage and inflammatory response. Ultimately, transcriptome sequencing and western blot analysis showed that Ccl5 activates the CCR5/PI3K/AKT/Nr4a1 pathway to increase the secretion of IL-12 and IFN-γ by DC cells, which then promotes the activation of effector T helper cells. Overall, these results indicate that Ccl5 significantly contributes to the progression of radon-induced lung damage by modulating DC to activate effector T helper cells.
Keywords: C-C motif chemokine ligand 5 (Ccl5); Dendritic cells; Effector T helper cells; Immune response; Lung injury; Radon.
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