A2AR limits IL-15-induced generation of CD39+ NK cells with high cytotoxicity

•Human circulating CD39+NK cells displayed higher capacity of degranulation.•The characteristic of CD39+ NK cells was stable in the setting of infection and cancer.•IL-15 promoted the generation of CD39+ NK cells.•A2AR suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. CD39-m...

Full description

Saved in:
Bibliographic Details
Published in:International immunopharmacology 2023-01, Vol.114, p.109567-109567, Article 109567
Main Authors: Kang, Guijie, Zhao, Xueqin, Sun, Jiafeng, Cheng, Chen, Wang, Cen, Tao, Longxiang, Zong, Lu, Yin, Wenwei, Cong, Jingjing, Li, Jing, Wang, Xuefu
Format: Article
Language:English
Subjects:
A2A adenosine receptor
CD39
Cytotoxicity
Cytotoxicity, Immunologic
Humans
IL-15
Interleukin-15
Killer Cells, Natural
NK cells
Receptor, Adenosine A2A - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Human circulating CD39+NK cells displayed higher capacity of degranulation.•The characteristic of CD39+ NK cells was stable in the setting of infection and cancer.•IL-15 promoted the generation of CD39+ NK cells.•A2AR suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39+ NK cells in humans are not known. We investigated the characteristics of human circulating CD39+ NK cells. In healthy donors, the proportion of circulating CD39+ NK cells in total NK cells was relatively low compared with that of CD39− NK cells. Nonetheless, a higher proportion of CD39+ NK cells expressed CD107a. Similarly, a higher proportion of CD39+ NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-γ and TNF-α, relative to CD39− NK cells. Importantly, IL-15 induced the generation of CD39+ NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39+ NK cells, which have a stronger cytotoxicity than CD39− NK cells. IL-15-induced human CD39+ NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2022.109567