NBIO Presents: Hernandez Moura Silva, PhD (Ragon Institute of MGH, MIT and Harvard)

Ironing Out the Ferrostatic Role of Vasculature Associated Macrophages

Iron is an essential micronutrient required by nearly all living organisms, and maintaining its homeostasis represents a fundamental biological challenge across multiple levels, from individual cells to entire tissues and the whole organism. We propose that local iron regulation within adipose tissue is centrally coordinated by vasculature-associated
macrophages (VAMs), a specialized population of resident tissue macrophages closely associated with the vasculature and known to perform key homeostatic functions. While VAMs and other resident tissue macrophages have been historically linked to host defense/innate immunity, there is a major gap in our understanding of their diverse functions beyond immunity, and how their dysfunction drives the progression of chronic inflammatory diseases. Gene expression profiling reveals that VAMs express a comprehensive suite of genes involved in iron import, export, processing, and storage. Our data further demonstrate that VAMs are the most efficient cell type within adipose tissue at importing transferrin-bound iron from the circulation and also function as significant intracellular iron reservoirs. Based on these findings, we demostrate that VAMs act as central regulators of adipose tissue iron content, continuously sensing local demand and modulating iron availability to support tissue homeostasis.