Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands
Lu Lu, Toshinobu Kuroishi, Yukinori Tanaka, Mutsumi Furukawa, Tomonori Nochi, Shunji Sugawara
Abstract
Abstract Gland macrophages are primed for gland development and functions through interactions within their niche. However, the phenotype, ontogeny, and function of steady-state salivary gland (SG) macrophages remain unclear. We herein identified CD11c + and CD11c − subsets among CD64 + macrophages in steady-state murine SGs. CD11c − macrophages were predominant in the SGs of embryonic and newborn mice and decreased with advancing age. CD11c + macrophages were rarely detected in the embryonic period, but rapidly expanded after birth. CD11c + , but not CD11c − , macrophage numbers decreased in mice treated with a CCR2 antagonist, suggesting that CD11c + macrophages accumulate from bone marrow-derived progenitors in a CCR2-dependent manner, whereas CD11c − macrophages were derived from embryonic progenitors in SGs. CD11c + and CD11c − macrophages strongly expressed colony-stimulating factor (CSF)-1 receptor, the injection of an anti-CSF-1 receptor blocking antibody markedly reduced both subsets, and SGs strongly expressed CSF-1, indicating the dependency of SG resident macrophage development on CSF-1. The phagocytic activity of SG macrophages was extremely weak; however, the gene expression profile of SG macrophages indicated that SG macrophages regulate gland development and functions in SGs. These results suggest that SG CD11c + and CD11c − macrophages are developed and instructed to perform SG-specific functions in steady-state SGs.