Thymic macrophages are the recycling hub mediating iron redistribution in the thymus via Ferroportin/Slc40a1 4625

Abstract Description Thymopoiesis is a complex process requiring gene recombination to generate pathogen recognition diversity and strict selection for self-tolerance. In the thymus, rapid cell proliferation and death occur simultaneously under a low-oxygen, nutrient-limited environment protected by the blood-thymus barrier to prevent autoimmunity. This study reveals that thymus-resident macrophages (TMΦs) play a crucial role beyond scavenging; they act as recycling centers. By engulfing Fe-rich dying thymocytes, TMΦs express Ferroportin (FPN) to efflux excess iron, which is reused by proliferating thymocytes. Deleting FPN in TMΦs disrupts Fe-recycling, leading to thymic atrophy, reduced peripheral T cells, and impaired T-cell responses to viral challenges. These findings emphasize TMΦs’ role in iron redistribution and immune regulation. Funding Sources Supported by MOST 110-2326-B-A49A-502-MY3, NSTC 112-2320-B-A49-013-MY3, and Cancer and Immunology Research Center NYCU, from the Higher Education Sprout Project by MOE to C.-L. Hsu. Topic Categories Hematopoiesis and Immune System Development (HEM)