Mammary intra-epithelial lymphocytes promote lactogenesis and offspring fitness

ABSTRACT: Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the adaptation of maternal physiology including the transformation of the mammary gland into a milk-secreting organ. How maternal immunity contributes to mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation during pregnancy is associated with thymic involution and a paradoxical enrichment in intraepithelial lymphocyte (IEL) precursors that no longer migrate to the gut, but instead preferentially accumulate within the mammary gland. Within this compartment, IEL precursors differentiate into T-bet-expressing unconventional CD8 lymphocytes with a cytotoxic signature which accumulate within the mammary epithelium in an IL-15-dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation and maturation of both contractile and milk-secreting cells, thereby promoting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy that is associated with mammary gland development and function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE280020 | GEO | 2025/06/04

REPOSITORIES: GEO