The ontogeny of mouse salivary gland macrophages is distinct between genders

Sexual dimorphism is found in gene expression and polarization of macrophages in mammals but remains unclear in the ontogeny of tissue-resident macrophages. Salivary glands show remarkable gender differences and macrophages here are essential for the maintenance of immune quiescence and tissue repair after damages. Therefore, we compared origins of macrophages in salivary glands between male and female mice using conditional Cx3cr1 and Ccr2 lineage tracing approaches. We found most salivary gland macrophages in adult males are locally maintained and derived from yolk sac progenitors or postnatal monocytes, whereas these cells in adult females are mostly short-lived and continuously replenished by monocytes. Female salivary glands also contain more monocytes and polarized macrophages. Cx3cr1 knockout made the macrophage ontogeny in adult male salivary glands like females. These gender differences appear related to female-dominant salivary gland phenotypes in a common autoimmune disease, Sjogren's syndrome, and need be considered in developing macrophage-targeting therapies of dry mouth caused by autoimmunity or radiation.