The Metabolic-Immune Axis: Amino Acids and Immune Cell Dynamics in Mammary Gland Development and Remodeling

The mammary gland undergoes tightly coordinated cycles of growth, differentiation and regression, which require precise communication between epithelial and stromal cells. Immune cells, whether tissue-resident or recruited, are well-established regulators of mammary development, which is orchestrated by hormones, cytokines, growth factors, microorganisms and nutritional signals. As essential building blocks for protein synthesis, amino acids modulate systemic metabolic homeostasis and influence the development, differentiation, and functional capacity of immune cells. However, the relationship between amino acid metabolism and immune regulation during mammary gland remodeling is not well understood. Here, we review the current understanding of the multiple biological factors underlying mammary gland development and remodeling, the composition and function of mammary immune cells across developmental stages, dynamic changes in mammary gland amino acids and transporters, and amino acid metabolism in the mammary gland and its immunomodulatory mechanisms. This improves our understanding of normal mammary biology and its implications for pathological conditions, such as lactation insufficiency and breast cancer.