Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy.
Sci Immunol
; 6(56)2021 02 19.
Article
em En
| MEDLINE
| ID: mdl-33617461
ABSTRACT
Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological response during the menstrual cycle and in pregnancy remains elusive. By surface proteome and transcriptome analysis as well as using humanized mice, we identify a differentiation pathway of uNK cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39. uNK cell differentiation occurred continuously in response to the endometrial regeneration and was driven by interleukin-15. Differentiated uNK cells displayed reduced proliferative capacity and immunomodulatory function including enhanced angiogenic capacity. By studying human uterus transplantation and monozygotic twins, we found that the uNK cell niche could be replenished from circulation and that it was under genetic control. Together, our study uncovers a continuous differentiation pathway of human NK cells in the uterus that is coupled to profound functional changes in response to local tissue regeneration and pregnancy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
/
Células Matadoras Naturais
/
Diferenciação Celular
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Endométrio
Tipo de estudo:
Observational_studies
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2021
Tipo de documento:
Article