Diverse myeloid cells are recruited to the developing and inflamed mammary gland.

Gerard J Graham,Gillian J Wilson,Francesca Vidler,Ayumi Fukuoka

doi:10.1111/imm.13430

Abstract

The immune system plays fundamental roles in the mammary gland, shaping developmental processes and controlling inflammation during infection and cancer.Here, we reveal unanticipated heterogeneity in the myeloid cell compartment duringdevelopment of virgin, pregnant, lactating and involuting mouse mammary glands,and in milk. We investigate the functional consequences of individual and compoundchemokine receptor deficiency on cell recruitment. Diverse myeloid cell recruitmentwas also shown in models of sterile inflammation and bacterial infection.Strikingly, we have shown that inflammation and infection can alter the abundanceof terminal end buds, a key developmental structure, within the pubertal mammarygland. This previously unknown effect of inflammatory burden during puberty couldhave important implications for understanding pubertal development.

Highlights

The mammary gland is a highly regenerative tissue within the body
Macrophages play an essential role in regulating mammary gland branching morphogenesis, as development is dramatically impaired in macrophage-deficient mice [3,4]
A detailed flow cytometric analysis was carried out to identify myeloid cell types using a defined panel of cell surface markers (Table 1, Supplemental Figures S1 and S2). t-SNE analysis carried out of CD45+ cells revealed distinct clusters corresponding to the cell types identified (Figure 1b)

Summary

INTRODUCTION

The mammary gland is a highly regenerative tissue within the body. It is unique, in that most of its development occurs postnatally throughout the female reproductive lifetime. Increased numbers of leukocytes, including neutrophils, monocytes and macrophages, are detected in the gland and in milk during mastitis [11,12] This impacts milk quality, leading to reduced infant weight gain and dysregulated immune development [13] and often leads to early cessation of breastfeeding. We reveal unanticipated heterogeneity in myeloid cells within the mammary gland at key developmental stages in virgin, pregnant, lactating and involuting mice. We have shown that inflammation and infection alter the number of TEBs, key developmental structures, within the pubertal mammary gland. This direct effect of inflammatory burden on pubertal development has not been reported previously

RESULTS

50 Ductal macrophage 40 30 20 10 10

DISCUSSION

METHODS