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. 2025 Mar 20;188(6):1662-1680.e24.
doi: 10.1016/j.cell.2025.01.028. Epub 2025 Feb 14.

Mammary intraepithelial lymphocytes promote lactogenesis and offspring fitness

Dan Corral  1 , Eduard Ansaldo  2 , Jérémie Delaleu  2 , Andrea C Pichler  3 , Juraj Kabat  4 , Cihan Oguz  5 , Ana Teijeiro  2 , Daniel Yong  2 , Mahnoor Abid  2 , Claudia A Rivera  2 , Verena M Link  2 , Katharine Yang  6 , Liang Chi  2 , Jia Nie  7 , Olena Kamenyeva  4 , Yiping Fan  8 , Jerry Kok Yen Chan  8 , Florent Ginhoux  9 , Rémy Bosselut  7 , Yasmine Belkaid  10
Affiliations

Mammary intraepithelial lymphocytes promote lactogenesis and offspring fitness

Dan Corral et al. Cell. .

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. IEL precursors differentiate into T-bet-expressing unconventional CD8αα lymphocytes in an IL-15-dependent manner. Mammary IELs control milk production by favoring the differentiation and maturation of contractile and milk-secreting cells, thereby promoting offspring fitness. Altogether, this work uncovers a contribution of the maternal adaptive immune system in organismal remodeling during pregnancy that is associated with mammary gland development and function.

Keywords: host physiology; intraepithelial lymphocytes; lactation; lactogenesis; mammary gland; offspring fitness; pregnancy; thymus; unconventional T cells.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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