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Updated: Jan 7, 2026
Author Spotlight: Studying Macrophage-Epithelial Cell Interactions in Salivary Gland Regeneration After Injury
Published on: November 17, 2023
Adenophages are an atypical macrophage population in exocrine glands sustained by ILC2-derived GM-CSF
Frederike Westermann1, Selma Tuzlak1, Victor Kreiner1
1Experimental Immunology, University of Zürich, Zurich, Switzerland.
Abstract:
Granulocyte-macrophage colony-stimulating factor (GM-CSF, Csf2) is a potent proinflammatory cytokine1. At steady state, however, GM-CSF has a distinct homeostatic function, being essential for the differentiation and maintenance of alveolar macrophages2-5. Whether macrophage development in nonpulmonary tissues is similarly dependent on GM-CSF is unclear. Here we examine developing tissues of GM-CSF fate-mapping and reporter mice6. We show that type 2 innate lymphoid cells (ILC2s) in the salivary glands produce GM-CSF and identify a macrophage subset that we refer to as 'adenophages'. Adenophages are noncanonical macrophages that are derived from fetal monocytes and are progressively replaced by monocyte-dendritic cell progenitor-derived monocytes. These cells form a spatial niche triad with GM-CSF-producing ILC2s and myoepithelial cells and are required for efficient secretion of saliva. Importantly, adenophages are present throughout exocrine glands, including lacrimal glands and mammary glands, and are also present in humans, indicating a conserved role in exocrine glands across species.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is crucial for salivary gland macrophages called adenophages. These cells, alongside ILC2s and myoepithelial cells, are vital for saliva secretion in humans and other species.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a known pro-inflammatory cytokine.
- GM-CSF plays a homeostatic role in maintaining alveolar macrophages in the lungs.
- The role of GM-CSF in macrophage development in non-pulmonary tissues remains largely unexplored.
Purpose of the Study:
- To investigate the role of GM-CSF in the development and function of macrophages in exocrine glands.
- To identify novel macrophage subsets and their cellular interactions within salivary glands.
Main Methods:
- Utilized GM-CSF fate-mapping and reporter mouse models.
- Examined macrophage populations and cellular niches in developing salivary glands.
- Investigated the presence and conservation of identified macrophage subsets in other exocrine glands and humans.
Main Results:
- Identified type 2 innate lymphoid cells (ILCs) in salivary glands as a source of GM-CSF.
- Discovered a novel macrophage subset, termed 'adenophages', derived from fetal monocytes.
- Demonstrated that adenophages form a critical niche with GM-CSF-producing ILCs and myoepithelial cells, essential for saliva secretion.
- Confirmed the presence of adenophages in lacrimal and mammary glands, and in human exocrine glands, indicating a conserved role.
Conclusions:
- GM-CSF is essential for the development and maintenance of adenophages in exocrine glands.
- Adenophages represent a distinct macrophage subset crucial for the function of salivary and other exocrine glands.
- The identified cellular interactions and macrophage populations highlight a conserved mechanism across species for exocrine gland homeostasis and function.
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