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

Lu Lu,Yukinori Tanaka,Toshinobu Kuroishi,Mutsumi Furukawa,Tomonori Nochi,Shunji Sugawara

doi:10.1038/s41598-022-04941-5

Lu Lu, Yukinori Tanaka + Show 4 more

Open Access

https://doi.org/10.1038/s41598-022-04941-5

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Journal: Scientific Reports	Publication Date: Jan 18, 2022
Citations: 11	License type: open-access

Affiliation: Tohoku University, Tohoku University Hospital

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.

Highlights

Gland macrophages are primed for gland development and functions through interactions within their niche
By combining the expression of CD64 and CD11c, CD45+MHC class II (MHCII)+ antigen-presenting cells (APCs) in submandibular glands (SMGs) were separated into CD64+ macrophages and C D64−CD11c+ classical DCs (cDCs) (Fig. 1a). CD64+ macrophages were further classified into the CD11c+ and CD11c− subsets
These results indicated that macrophages exist as predominant APCs in the steady-state salivary gland (SG) of adult mice and that SG macrophages comprise C D11c+ and C D11c− subsets, which may have different ontogenies and functions

Summary

Introduction

Gland macrophages are primed for gland development and functions through interactions within their niche. We identified CD11c+ and CD11c− subsets among CD64+ macrophages in steady-state murine SGs. The phagocytic activity of SG macrophages was extremely weak; the gene expression profile of SG macrophages indicated that SG macrophages regulate gland development and functions in SGs. The phagocytic activity of SG macrophages was extremely weak; 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. Macrophages, monocytes, and dendritic cells (DCs) are members of the mononuclear phagocyte system, which exhibits multifunctional immune responses, and tissue-resident macrophages have a wide variety of functions in mammalian tissues[1,2,3]. Hematopoietic stem cell (HSC)-derived monocytes that emerge from the fetal liver contribute to the long-lived macrophage pool at birth while adult hematopoiesis is only starting in the bone marrow (BM)[10]. In the course of these studies, we found that C D64+ macrophages in SGs comprised CD11c+ and CD11c− subsets[17]

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