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Updated: Nov 21, 2025
Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Does tissue imprinting restrict macrophage plasticity?
Martin Guilliams1,2, Freya R Svedberg3,4
1Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB Center for Inflammation Research, Ghent, Belgium. martin.guilliams@ugent.vib.be.
Abstract:
Macrophages have long been considered as particularly plastic cells. However, recent work combining fate mapping, single-cell transcriptomics and epigenetics has undermined the macrophage plasticity dogma. Here, we discuss recent studies that have carefully dissected the response of individual macrophage subsets to pulmonary insults and call for an adjustment of the macrophage plasticity concept. We hypothesize that prolonged tissue residency shuts down much of the plasticity of macrophages and propose that the restricted plasticity of resident macrophages has been favored by evolution to safeguard tissue homeostasis. Recruited monocytes are more plastic and their differentiation into resident macrophages during inflammation can result in a dual imprinting from both the ongoing inflammation and the macrophage niche. This results in inflammation-imprinted resident macrophages, and we speculate that rewired niche circuits could maintain this inflammatory state. We believe that this revisited plasticity model offers opportunities to reset the macrophage pool after a severe inflammatory episode.
Insights
Resident macrophages exhibit limited plasticity due to prolonged tissue residency, challenging the traditional view. This restricted plasticity, particularly in inflammation-imprinted cells, may safeguard tissue homeostasis and offer therapeutic reset opportunities.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Macrophages are traditionally viewed as highly plastic immune cells.
- Recent advances in cell biology challenge this long-held dogma.
- Understanding macrophage plasticity is crucial for tissue homeostasis.
Purpose of the Study:
- To reassess the concept of macrophage plasticity in light of new evidence.
- To investigate the plasticity of different macrophage subsets in pulmonary insults.
- To propose a revised model of macrophage plasticity.
Main Methods:
- Fate mapping studies
- Single-cell transcriptomics
- Epigenetic analyses
- Dissection of macrophage subset responses to pulmonary insults
Main Results:
- Prolonged tissue residency significantly reduces macrophage plasticity.
- Recruited monocytes display greater plasticity than resident macrophages.
- Inflammation and niche interactions imprint recruited monocytes, creating inflammation-imprinted resident macrophages.
- Rewired niche circuits may sustain the inflammatory state of these imprinted macrophages.
Conclusions:
- The plasticity of macrophages is more restricted than previously thought, especially for resident populations.
- Restricted plasticity in resident macrophages likely evolved to maintain tissue homeostasis.
- A revised plasticity model, considering dual imprinting, offers new avenues for therapeutic intervention in inflammatory conditions.
