Systemically administered silica nanoparticles result in diminished T cell response in lung

In the context of nanomedicine, the inevitable accumulation of systemically administered inorganic nanomaterials in normal tissues and organs (e.g. liver, lung, spleen) may inadvertently perturb the normal immune microenvironment. Here, we investigate the immune microenvironment of the lung, liver, and spleen following the systemic administration of silica nanoparticles (SiO2 NPs). Using single-cell RNA sequencing technology, we observe a dramatic decrease in the number of T cells in the lung following SiO2 NPs administration, coupled to the enhanced IL-17-producing γδ T cells frequency, the reduced αβ T population, as well as the greater expression of the T cells dysfunctional markers. We further find that this effect is caused by accumulation of bone-marrow-derived cells in the lung, which are recruited by the SiO2 NPs. Unexpectedly, in multiple mouse models, tumor metastasis in the lung is found more easily in SiO2-treated mice. Our results indicate that systemically administered SiO2 NPs may inadvertently perturb normal lung microenvironment characterized by T cell-dysfunction signature, which increases the likelihood of malignant cells survival in the lung tissue.