Mapping NK cell diversity in response to COVID-19 and mRNA vaccination

Kishi, Yosuke; Liu, Yu-Chen; Ishikawa, Masakazu et al.

Scientific Reports, 2025, 15, 37577

Number of Access:122（2025-12-09 23:05 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102938

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Title
Mapping NK cell diversity in response to COVID-19 and mRNA vaccination
Creator
CreatorName
Kishi, Yosuke
NRID
1000050894698 1000050894698
ORCID
0000-0002-2750-0182 0000-0002-2750-0182
researchmap permalink
liuyuchen liuyuchen
CreatorName
Liu, Yu-Chen
NRID
1000010897028 1000010897028
CreatorName
Ishikawa, Masakazu
CreatorName
Yamashita, Maika
NRID
1000070644003 1000070644003
ORCID
0000-0001-5771-570X 0000-0001-5771-570X
researchmap permalink
38283828 38283828
Scopus Author ID
36632584800 36632584800
CreatorName
Matsumoto, Hisatake
NRID
1000070301265 1000070301265
researchmap permalink
read0054647 read0054647
Scopus Author ID
7202495132 7202495132
CreatorName
Ogura, Hiroshi
NRID
1000010618838 1000010618838
ORCID
0000-0003-3157-5870 0000-0003-3157-5870
researchmap permalink
SSakakibara SSakakibara
CreatorName
Sakakibara, Shuhei
NRID
1000000346131 1000000346131
ORCID
0000-0002-4552-783X 0000-0002-4552-783X
researchmap permalink
read0092307 read0092307
Scopus Author ID
6506703054 6506703054
CreatorName
Okuzaki, Daisuke
Subject
NK cells
COVID-19
mRNA vaccine
scRNA-seq
Trajectory analysis
Description
Kishi Yosuke, Liu Yu-Chen, Ishikawa Masakazu, et al. Mapping NK cell diversity in response to COVID-19 and mRNA vaccination. Scientific Reports 15, 37577 (2025); https://doi.org/10.1038/S41598-025-11575-W.
Abstract
Human NK cells exhibit functional heterogeneity, yet the clinical conditions and cellular processes driving this diversity remain insufficiently understood. Here, we report that NK cell diversity emerges during peripheral development, influenced by the divergence of adaptive NK cells from various stages of canonical NK cell maturation during the resolution phase of severe COVID-19. Using scRNA-seq, we analyzed blood NK cells from patients with severe COVID-19 (acute phase and post-intensive care), individuals vaccinated with the SARS-CoV-2 mRNA vaccine (BNT162b2), and healthy donors. The frequencies of immature CD56ᵇʳⁱᵍʰᵗ and proliferating NK cells increased following BNT162b2 vaccination. In contrast, the frequency of adaptive CD56ᵈⁱᵐ cells was markedly elevated in patients recovering from severe COVID-19, alongside clonal expansion and enhanced mitochondrial oxidative phosphorylation. Trajectory analysis revealed a bifurcation in peripheral NK cell development, with CD56ᵇʳⁱᵍʰᵗ cells diverging into canonical and adaptive CD56ᵈⁱᵐ subsets during the course of severe COVID-19. Notably, adaptive NK differentiation exhibited transcriptional and signaling profiles analogous to those of T-cell activation. Thus, NK cell diversity is shaped by the induction of an intrinsic adaptive program. These findings uncover the mechanisms underlying NK cell heterogeneity and have implications for medical applications, including the development of immunotherapies that leverage adaptive NK cell functions.
Publisher
Springer Science and Business Media LLC
Source Title
Scientific Reports
Volume (Issue)
15
Page
37577
Date of Issued
2025-10-28
Language
English
Handle URL
https://hdl.handle.net/11094/102938
eISSN
20452322
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1038/S41598-025-11575-W
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article