Abstract

Iron is an essential element for multiple fundamental biological processes required for life; yet iron overload can be cytotoxic. Consequently, iron concentrations at the cellular and tissue level must be exquisitely governed by mechanisms that complement and fine-tune systemic control. It is well appreciated that macrophages are vital for systemic iron homeostasis, supplying or sequestering iron as needed for erythropoiesis or bacteriostasis, respectively. Indeed, recycling of iron through erythrophagocytosis by splenic macrophages is a major contributor to systemic iron homeostasis. However, accumulating evidence suggests that tissue-resident macrophages regulate local iron availability and modulate the tissue microenvironment, contributing to cellular and tissue function. Here, we summarize the significance of tissue-specific regulation of iron availability and highlight how resident macrophages are critical for this process. This tissue-dependent regulation has broad implications for understanding both resident macrophage function and tissue iron homeostasis in health and disease.

Highlights

  • Iron is an essential element for various fundamental biological processes necessary for life

  • A postulate gaining traction is that tissue Mɸs are so-called ferrostats that sense and respond to local tissue iron needs, thereby regulating the tissue microenvironment. One example of this tenet is a specialized population of adipose tissue (AT) Mɸs (ATMɸs) — previously identified by our group — that are iron-rich (MFehi) and have the intrinsic capacity to take up excess iron, and thereby protect adipocytes from iron overload [17, 18]

  • Data indicate that in addition to patrolling for changes in systemic iron levels, resident Mɸs are critical in handling iron at the local tissue level

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Summary

Introduction

Iron is an essential element for various fundamental biological processes necessary for life. A postulate gaining traction is that tissue Mɸs are so-called ferrostats that sense and respond to local tissue iron needs, thereby regulating the tissue microenvironment One example of this tenet is a specialized population of adipose tissue (AT) Mɸs (ATMɸs) — previously identified by our group — that are iron-rich (MFehi) and have the intrinsic capacity to take up excess iron, and thereby protect adipocytes from iron overload [17, 18]. Ited to AT, and mounting evidence reveals their presence and homeostatic functions in multiple tissues and organs This Review highlights the importance of tissue-specific regulation of iron availability and summarizes how resident Mɸs are fundamental to this homeostatic circuit

Overview of Mɸ iron flux
Mɸ polarization and iron handling
Tissue Mɸs regulate iron homeostasis and tissue function
Concluding remarks
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