Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy
| Autor: | Antonio Lentini, Natalie Sleiers, Benedikt Strunz, Bogdan Dumitrescu, Niklas K. Björkström, Martin Cornillet, Sebastian Gidlöf, Björn Reinius, Jonna Bister, Tim Willinger, Mats Brännström, Ylva Crona-Guterstam, Hanna Jönsson, Martin A. Ivarsson, Egle Kvedaraite, Iva Filipovic, Russell S. Hamilton |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Cell Population Mice Transgenic Biology Lymphocyte Activation Transcriptome 03 medical and health sciences Endometrium Mice 0302 clinical medicine Immune system Pregnancy medicine Human Umbilical Vein Endothelial Cells Animals Humans Regeneration Gene Knock-In Techniques Longitudinal Studies Receptors Immunologic Receptor education Menstrual Cycle Progesterone Interleukin-15 education.field_of_study Innate immune system Regeneration (biology) Cell Differentiation General Medicine Antigens Differentiation Healthy Volunteers Cell biology Transplantation Killer Cells Natural 030104 developmental biology medicine.anatomical_structure embryonic structures Female 030215 immunology |
| Zdroj: | Science immunology. 6(56) |
| ISSN: | 2470-9468 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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