Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands

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.