Macrophage Iron Metabolism in Allografts and Tumors

ABSTRACT Macrophages are present at high frequencies in transplanted organs and solid tumors. These infiltrating macrophages are highly tuned by tissue niche signals. However, the underlying mechanisms that orchestrate the activation of distinct macrophage populations remain unclear. Here, using heart transplantation and tumor implantation models, we found that macrophages in cardiac allografts exhibited higher intracellular iron (Fe 2+ ) level and higher expression of the iron transporter SLC11A1 than those in the solid tumors. In mice, the myeloid-specific deletion of Slc11a1 alleviated the proinflammatory state of macrophages and cardiac allografts rejection. Together, our findings identify SLC11A1 as a new player in immune response regulation, implicating SLC11A1 as a therapeutic target for both allograft and tumor rejection. This preprint reports initial findings; additional experiments are ongoing and will be included in a future full manuscript.