The maternal immune system regulates lactation by differentiating the mammary glands during pregnancy. A specific population of lymphocytes promotes milk production and ejection, thereby improving the health of newborns. This discovery highlights the importance of maternal immune status and opens new avenues for addressing lactation challenges. The study was conducted by a team from the NIAID (NIH, USA) led by Prof. Yasmine Belkaid, now President of the Institut Pasteur (Paris).
Scientists have made a major discovery about lactation regulation. The study shows that the maternal immune system plays a key role in the differentiation of the mammary glands (the organ responsible for milk secretion) during pregnancy, thus enabling optimal lactation and newborn growth. This work was led and funded by the National Institute of Allergy and Infectious Diseases (NIAID, NIH, Bethesda, USA), in the laboratory directed by Prof. Yasmine Belkaid, who is now the President of the Institut Pasteur (Paris, France).
Understanding lactation mechanisms
Pregnancy represents a unique physiological state that requires extensive remodeling of the organism to support fetal development. Metabolic adjustments are thus necessary to ensure adequate energy supply for fetal growth, maintenance of maternal homeostasis – the process by which the mother's body maintains internal stability despite external changes – and preparation for lactation. Indeed, during pregnancy, the mammary glands undergo massive remodeling to become a milk-secreting organ and thus meet the nutritional needs of the newborn from birth.
Lactation is a crucial process that ensures newborns receive the nutrition and immune protection they need to develop healthily. Until now, the precise mechanisms regulating this development were not fully understood.
The maternal immune system regulates mammary gland differentiation during pregnancy
A recent study conducted by Dan Corral, PhD, a postdoctoral researcher in Prof. Yasmine Belkaid's laboratory at NIAID (NIH, Bethesda, USA), shows that for the first time, this process of mammary gland development during pregnancy is regulated by the maternal immune system, which promotes optimal lactation and thus newborn growth. The team identified unconventional T lymphocytes, i.e., immune cells that possess characteristics or functions different from classical T. These non-conventional lymphocytes accumulate and differentiate within the mammary glands during pregnancy in close interaction with milk-secreting cells and contractile cells facilitating milk ejection.
The researchers identified that this population of cells originates from a thymic self-reactive precursor, enriched in the thymus (the organ responsible for T lymphocyte development) during pregnancy and migrating to the mammary glands. The NIAID researchers thus showed that the presence of unconventional lymphocytes is sufficient to induce mammary gland development, promoting the differentiation of milk-secreting cells and improving the contraction of mammary contractile cells, allowing for increased milk production. Furthermore, a similar population was also identified in human breast milk samples, suggesting that these cells could be conserved across all mammalian species.
Understanding vulnerability to inflammation and milk production delays...
The work of Dan Corral and Yasmine Belkaid reveals that optimal lactation also depends on maternal immunity, highlighting a potential vulnerability to maternal immune status and inflammatory challenges. Some mothers experience lactation impairment or failure, which can lead to breastfeeding difficulties and impact the child's health.
It remains to be determined to what extent environmental factors, such as diet or infections, or hereditary immune deficiencies have an impact on lactogenesis.
Source
Mammary intraepithelial lymphocytes promote lactogenesis and offspring fitness, Cell, February 14, 2025.
doi.org/10.1016/j.cell.2025.01.028
