Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis.

Hanasoge Somasundara, Amritha Varshini, Moss, Matthew A, Feigman, Mary J, Chen, Chen, Cyrill, Samantha L, Ciccone, Michael F, Trousdell, Marygrace C, Vollbrecht, Macy, Li, Siran, Kendall, Jude, Beyaz, Semir, Wilkinson, John E, Dos Santos, Camila O (December 2021) Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis. Cell Reports, 37 (10). p. 110099. ISSN 2211-1247

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Abstract

Pregnancy reprograms mammary epithelial cells (MECs) to control their responses to pregnancy hormone re-exposure and carcinoma progression. However, the influence of pregnancy on the mammary microenvironment is less clear. Here, we used single-cell RNA sequencing to profile the composition of epithelial and non-epithelial cells in mammary tissue from nulliparous and parous female mice. Our analysis indicates an expansion of γδ natural killer T-like immune cells (NKTs) following pregnancy and upregulation of immune signaling molecules in post-pregnancy MECs. We show that expansion of NKTs following pregnancy is due to elevated expression of the antigen-presenting molecule CD1d on MECs. Loss of CD1d expression on post-pregnancy MECs, or overall lack of activated NKTs, results in mammary oncogenesis. Collectively, our findings illustrate how pregnancy-induced changes modulate the communication between MECs and the immune microenvironment and establish a causal link between pregnancy, the immune microenvironment, and mammary oncogenesis.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells diseases & disorders > pregnancy diseases & disorders > cancer > drugs and therapies > tumor microenvironment
CSHL Authors:	Feigman, Mary J. Chen, Chen Cyrill, Samantha L Ciccone, Michael F Trousdell, Marygrace C Li, Siran Kendall, Jude T. Beyaz, Semir Dos Santos, Camila O. Hanasoge Somasundara, Amritha Varshini
Communities:	CSHL labs > Beyaz lab CSHL labs > Dos Santos lab CSHL labs > Wigler lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	7 December 2021
Date Deposited:	15 Dec 2021 17:09
Last Modified:	31 May 2022 20:53
PMCID:	PMC8719356
URI:	https://repository.cshl.edu/id/eprint/40460

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