Adenophages are an atypical macrophage population in exocrine glands sustained by ILC2-derived GM-CSF
Granulocyte-macrophage colony-stimulating factor (GM-CSF, Csf2) is a potent proinflammatory cytokine. At steady state, however, GM-CSF has a distinct homeostatic function, being essential for the differentiation and maintenance of alveolar macrophages. 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 mice. 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.
Authors
- Ricardo Fróis-Martins (ORCID: https://orcid.org/0000-0002-7338-2383)
- Myrto Andreadou (ORCID: https://orcid.org/0000-0001-6757-4664)
- Stoyan Ivanov (ORCID: https://orcid.org/0000-0002-0527-2297)
- E. Roussel (ORCID: https://orcid.org/0000-0003-0158-2105)
- Melanie Greter (ORCID: https://orcid.org/0000-0002-7220-5369)
- Gioana Litscher
- Sònia Tugues (ORCID: https://orcid.org/0000-0003-1206-3386)
- David Alejandro Bejarano (ORCID: https://orcid.org/0000-0001-7804-0131)
- Kathy D. McCoy (ORCID: https://orcid.org/0000-0002-3900-9227)
- Colin Sparano (ORCID: https://orcid.org/0000-0003-0776-6896)
- Mitchell Bijnen (ORCID: https://orcid.org/0000-0003-2781-8702)
- Iain J. Nixon (ORCID: https://orcid.org/0000-0002-8919-8783)
- Calum C. Bain (ORCID: https://orcid.org/0000-0001-8884-327X)
- Rachel Chanel Lindemann (ORCID: https://orcid.org/0000-0002-6175-2084)
- Andreas Schlitzer (ORCID: https://orcid.org/0000-0001-7662-3712)
- Frederike Westermann (ORCID: https://orcid.org/0000-0002-3253-2322)
- Donatella DeFeo
- Salomé LeibundGut-Landmann
- Alexandre Gallerand
- Laura Mercedes Oberbichler
- Hannah van Hove
- et al.
- Christoph Schneider
- Florent Ginhoux
- Burkhard Becher
- Aline Ignacio
- Virginia Cecconi
- Victor Linus Kreiner
- Anja Kipar
- Zhaoyuan Liu
- Haiting Wang
- Selma Tuzlak
Publication Details
- Journal
- Universität Zürich, ZORA
- Published
- 2026-01-01
- DOI
- https://doi.org/10.5167/uzh-293097
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00