Abstract
Abstract Breastfeeding has long been associated with health benefits for the infant. Breast milk is composed of essential nutrients and bioactive molecules shaping the growth, and the immune development of the offspring. An optimal development of the mammary gland (MG) during pregnancy is critical to maintaining the beneficial effects of lactation. Nevertheless, how the lactation process is regulated by the immune system remains largely unexplored. Our data reveal that the commitment of mammary epithelial cells into milk-secreting cells is associated with the accumulation of T-bet +lymphoid cells, preferentially localized at the proximity and inside the mammary epithelium. Among mammary T-bet +cells, we characterized an unconventional T cell population exhibiting common features with gut CD8αα +intra-epithelial lymphocytes and deriving from the same thymic progenitor. Such process is associated with thymus involution during pregnancy and specific enrichment in thymic precursor that preferentially migrates into the MG during pregnancy. These cells promote milk production and expression of β-casein, one of the main milk protein, resulting in an increase in newborn weight. This work uncovers a previously unappreciated contribution for the adaptive immune system in mammary gland development and lactation. Decoding the immune regulation of the MG will allow to understand the profound transformation of this compartment as a primary nutritional source for the offspring and may allow to understand how dysregulation of this process could affect the long-term development of newborns. This work was supported in part by intramural funds of NIAID, NIH.
Published Version
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