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Maternal intra-epithelial lymphocytes support lactogenesis and offspring fitness

ABSTRACT: Maternal intra-epithelial lymphocytes support lactogenesis and offspring fitness

PROVIDER: PRJNA1068069 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27697286.fastq.gz	Fastqsanger.gz
	SRR27697287.fastq.gz	Fastqsanger.gz
	SRR27697288.fastq.gz	Fastqsanger.gz
	SRR27697289.fastq.gz	Fastqsanger.gz
	SRR27697290.fastq.gz	Fastqsanger.gz

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Maternal intra-epithelial lymphocytes support lactogenesis and offspring fitness

Project description:Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the remodeling of maternal physiology including the transformation of mammary gland into milk-secreting organ. While adaptive immunity has been associated with the broad control of host physiology, how maternal immunity contributes to organismal remodeling during pregnancy including 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 to pregnancy is associated with thymic involution and paradoxical enrichment in intraepithelial lymphocyte precursors that no longer migrate to the gut but preferentially accumulate within the mammary gland. Within this compartment the precursors develop as T-bet expressing lymphocytes accumulating within the mammary epithelium in an IL-15 dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation of both contractile and milk-secreting cells, thereby affecting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy associated with mammary gland development and function.

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Mammary intra-epithelial lymphocytes promote lactogenesis and offspring fitness

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Mammary intra-epithelial lymphocytes promote lactogenesis and offspring fitness

Project description: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.

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Project description:To test the role of intraepithelial lymphocytes in mammay grand epithelial function during pregnancy we performed single cell RNA sequencing of epithelial and myoepithelial cells from the mammary gland in WT mice, Raggc-KO mice, Raggc-KO mice adaptively transferred with IEL precursors.

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Project description:T cells accumulate in the mammary gland during pregnancy and lactation. In order to understand the diversity, transcriptional states, TCR repertoire, and function of mammary gland T cells, and how these change during pregnancy and lactation compared to homeostasis, we performed single cell RNA sequencing on mammary gland T cells in mice.

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