IRF2 is required for development and functional maturation of human NK cells.
IRF2
NK cell biology
NK cell development
human NK cells
transcription factor
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
07
09
2022
accepted:
11
11
2022
entrez:
22
12
2022
pubmed:
23
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Natural killer (NK) cells are cytotoxic and cytokine-producing lymphocytes that play an important role in the first line of defense against malignant or virus-infected cells. A better understanding of the transcriptional regulation of human NK cell differentiation is crucial to improve the efficacy of NK cell-mediated immunotherapy for cancer treatment. Here, we studied the role of the transcription factor interferon regulatory factor (IRF) 2 in human NK cell differentiation by stable knockdown or overexpression in cord blood hematopoietic stem cells and investigated its effect on development and function of the NK cell progeny. IRF2 overexpression had limited effects in these processes, indicating that endogenous IRF2 expression levels are sufficient. However, IRF2 knockdown greatly reduced the cell numbers of all early differentiation stages, resulting in decimated NK cell numbers. This was not caused by increased apoptosis, but by decreased proliferation. Expression of IRF2 is also required for functional maturation of NK cells, as the remaining NK cells after silencing of IRF2 had a less mature phenotype and showed decreased cytotoxic potential, as well as a greatly reduced cytokine secretion. Thus, IRF2 plays an important role during development and functional maturation of human NK cells.
Identifiants
pubmed: 36544762
doi: 10.3389/fimmu.2022.1038821
pmc: PMC9762550
doi:
Substances chimiques
Transcription Factors
0
Cytokines
0
IRF2 protein, human
0
Interferon Regulatory Factor-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1038821Informations de copyright
Copyright © 2022 Persyn, Wahlen, Kiekens, Van Loocke, Siwe, Van Ammel, De Vos, Van Nieuwerburgh, Matthys, Taghon, Vandekerckhove, Van Vlierberghe and Leclercq.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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