Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice.

Ying Wang,Heather L Machado,Patrice M Witschen,Danielle N Huggins,Thomas S Chaffee,Kathryn L Schwertfeger,Ayman M Ibrahim,Rebecca S Larue,Andrew C Nelson

doi:10.7554/elife.57438

Ying Wang, Heather L Machado + Show 7 more

Open Access

https://doi.org/10.7554/elife.57438

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Journal: eLife	Publication Date: Jun 1, 2020
Citations: 60	License type: CC BY 4.0

Affiliation: Tulane University, University of Minnesota, Cairo University

Abstract

Tissue-resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. Macrophages have been linked to ductal development in the virgin mammary gland, but less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single-cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland that is characterized by the expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan. This subpopulation is enriched in genes associated with ECM remodeling and is specifically associated with hyaluronan-rich regions within the adipose stroma and fibrous capsule of the virgin mammary gland. Furthermore, macrophage depletion leads to enhanced accumulation of hyaluronan-associated ECM in the adipose-associated stroma, indicating that resident macrophages are important for maintaining homeostasis within the nulliparous mammary gland stroma.

Highlights

Tissue-resident macrophages have been ascribed various functions, including immune surveillance and phagocytosis of apoptotic debris (Davies et al, 2013)
Further analysis was performed to determine the presence of Lyve-1+ macrophages in the mammary gland, which demonstrated that approximately 35% of CD45+CD11b+F4/80+ cells within mammary glands are Lyve-1+ (Figure 1B, Figure 1—figure supplement 1B)
Despite the presence of HA surrounding the terminal end buds (TEBs), few Lyve-1+F4/80+ cells are found within the TEBassociated stroma (Figure 1C), we focused on the extracellular matrix (ECM)-rich regions within the adipose stroma

Summary

Introduction

Tissue-resident macrophages have been ascribed various functions, including immune surveillance and phagocytosis of apoptotic debris (Davies et al, 2013). Depending upon the site of localization, these macrophages can exhibit additional tissue-specific behaviors, such as the regulation of surfactant by alveolar macrophages in the lung and of neuronal function by microglia in the brain (Haldar et al, 2014). These tissue-specific functions are thought to be driven in response to factors within the local tissue microenvironment.

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