Developing exocrine glands harbour a distinct macrophage population that is maintained by ILC2 derived GM-CSF [bulk RNA-seq]

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has a non-redundant role in the emergence and maintenance of alveolar macrophages (AMs). However, its role in steady-state myelopoiesis outside the lung is largely unexplored. We discovered a strong signal of GM-CSF production by type 2 innate lymphoid cells (ILC2s) in the developing salivary glands (SG). ILC2 derived GM-CSF fosters the development of a hitherto undescribed phagocyte subset, which we named adenophages. Detailed analysis focusing on phenotypic and transcriptional profiling revealed that adenophages represent a non-canonical macrophage subset displaying shared aspects of both, macrophages and dendritic cells. We found them to be homogenously distributed across the SG, but always forming a niche-triad with GM-CSF producing ILC2s and myoepithelial cells. Importantly, adenophages were present throughout all analyzed exocrine glands such as lacrimal glands and mammary glands, and were also identified in human SG, indicating a conserved role in exocrine glands across species. Overall design: Myoepithelial cells were facs sorted from the salivary glands of 1 month old Csf2-KO (N=4) or Control (N=4) mice (male and female) and RNA-seq was performed