Inflammation and accompanied disrupted hematopoiesis in adult mouse induced by rare earth element nanoparticles

Rare earth element nanoparticles (REE NPs) or agents have been used extensively in various fields. Human exposure to REE NPs is an increasing concern. To date, REE NP-mediated comprehensive immune responses after incorporation into the body remain unclear. In our study, using gadolinium oxide NPs (Gd₂O₃) as a typical REE NP, we systematically investigated immune responses in vivo. The liver and spleen were the main sites where Gd₂O₃ retained and accumulated, while Gd₂O₃ content per unit tissue mass in the spleen was 4.4 times higher than that in the liver. Gd₂O₃ increased the number of monocyte-derived macrophages and myeloid-derived dendritic cells (M-DCs) in the liver. In the spleen, Gd₂O₃ caused infiltration of neutrophils, M-DCs, and B cells. The accumulation of Gd₂O₃ in the liver or spleen also contributed to an increased concentration of cytokines in peripheral blood. In both the bone marrow and spleen, Gd₂O₃ led to increased populations of hematopoietic stem cells (HSCs), multipotent progenitors, and common lymphoid progenitors. Compared to the decreased monocytes in peripheral blood on day 2, a significant decrease of circulating lymphocytes on day 7 was still observed, suggesting the exposure duration led to variable effects. This might be explained by the sustained accumulation of Gd₂O₃ in the liver and spleen. Together, our study systemically depicted the alterations in mature immune alterations together with hematopoiesis in both myeloid and lymphoid lineages induced by Gd₂O₃ exposure. Our findings will facilitate a comprehensive understanding of the interactions of immune system with REE NPs in vivo.