Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis.
Animals
Antigens, CD1d
/ metabolism
Cell Communication
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Epithelial Cells
/ immunology
Female
Gene Expression Regulation, Neoplastic
Genes, BRCA1
Genes, myc
Lymphocyte Activation
Mammary Glands, Animal
/ immunology
Mammary Neoplasms, Experimental
/ genetics
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Natural Killer T-Cells
/ immunology
Parity
Pregnancy
Receptors, Antigen, T-Cell, gamma-delta
/ metabolism
Signal Transduction
Tumor Microenvironment
Brca1 KO
CD1d
NKT cells
mammary development
pregnancy
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
received:
15
03
2021
revised:
25
08
2021
accepted:
15
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34879282
pii: S2211-1247(21)01593-X
doi: 10.1016/j.celrep.2021.110099
pmc: PMC8719356
mid: NIHMS1762846
pii:
doi:
Substances chimiques
Antigens, CD1d
0
CD1d antigen, mouse
0
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110099Subventions
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG069727
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248158
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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