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.
