AI Summary
This article explores the versatile roles of resident tissue macrophages (RTMs) beyond immune defense. It highlights that RTMs play a crucial role in maintaining tissue homeostasis and are impacted by the tissue microenvironment, affecting their differentiation and function. The review also discusses the division of labor among RTM subsets and their dysfunction in disease. Overall, the study sheds light on the complex nature of RTMs and their significance beyond traditional immunological functions.
A recent study published in Science Immunology summarized the role of resident tissue macrophages (RTMs) in homeostasis and disease.
Study: Resident tissue macrophages: Key coordinators of tissue homeostasis beyond immunity. Image Credit: ART-ur/Shutterstock.com
Background
Macrophages are evolutionarily conserved phagocytes ubiquitously present in almost all organs and tissues. It is recognized that the umbrella term macrophage comprises highly heterogeneous cells with diverse functions and roles.
RTMs are stable, long-lived subpopulations in different organs and tissues and have been linked to innate immunity and the pathogenesis of chronic inflammatory diseases. However, RTMs have broader functions beyond immunity.
Recently, exploring RTM subsets to functional, developmental, and spatial levels has become feasible, helping identify mechanisms of tissue homeostasis.
Notwithstanding these advances, substantial knowledge gaps remain. In the present review, researchers provided insights into conditions impacting RTM identity, division of labor among RTM subsets, and RTM dysfunction in disease.
Tissue microenvironment impacts RTM development
RTMs originate from embryonic progenitors or hematopoietic stem cell (HSC)-derived monocytes. The local microenvironment influences the trajectories of RTM differentiation upon seeding a tissue. In homeostasis, the local environmental cues shape RTM cell identity in a tissue-specific manner.
Further, the phenotypic and functional convergence of HSC-derived monocytes towards a tissue-specific RTM program is driven by the local environment.
However, inflammation or disease markedly impacts their differentiation. During such disturbance, the differentiation of HSC-derived monocytes skews toward pro-reparative, tumor-supportive, or pro-inflammatory phenotypes, differing from that of steady-state RTMs.
These inflammation-associated macrophages (iMacs) are short-lived, and upon resolution (of the disturbance), the tissue transitions