Zeb2 regulates differentiation of long-lived effector of invariant natural killer T cells

After activation, some invariant natural killer T (iNKT) cells are differentiated into Klrg1 + long-lived effector NKT1 cells. However, the regulation from the effector phase to the memory phase has not been elucidated. Zeb2 is a zinc finger E homeobox-binding transcription factor and is expressed i...

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Bibliographic Details
Published in:Communications biology 2023-10, Vol.6 (1), p.1070-1070, Article 1070
Main Authors: Iyoda, Tomonori, Shimizu, Kanako, Endo, Takaho, Watanabe, Takashi, Taniuchi, Ichiro, Aoshima, Honoka, Satoh, Mikiko, Nakazato, Hiroshi, Yamasaki, Satoru, Fujii, Shin-ichiro
Format: Article
Language:English
Subjects:
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Apoptosis
Biology
Biomedical and Life Sciences
Cell activation
Cell differentiation
Cells
Cooperation
CX3CR1 protein
Cytokines
Effector cells
Gene expression
Gene regulation
Homeobox
KLRG1 protein
Life Sciences
Lymphocytes
Lymphocytes T
Natural killer cells
Spleen
Thymus gland
Transcription factors
Zinc finger proteins
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Summary:After activation, some invariant natural killer T (iNKT) cells are differentiated into Klrg1 + long-lived effector NKT1 cells. However, the regulation from the effector phase to the memory phase has not been elucidated. Zeb2 is a zinc finger E homeobox-binding transcription factor and is expressed in a variety of immune cells, but its function in iNKT cell differentiation remains also unknown. Here, we show that Zeb2 is dispensable for development of iNKT cells in the thymus and their maintenance in steady state peripheral tissues. After ligand stimulation, Zeb2 plays essential roles in the differentiation to and maintenance of Klrg1 + Cx3cr1 + GzmA + iNKT cell population derived from the NKT1 subset. Our results including single-cell-RNA-seq analysis indicate that Zeb2 regulates Klrg1 + long-lived iNKT cell differentiation by preventing apoptosis. Collectively, this study reveals the crucial transcriptional regulation by Zeb2 in establishment of the memory iNKT phase through driving differentiation of Klrg1 + Cx3cr1 + GzmA + iNKT population. Zeb2 is critical for the establishment of Klrg1 + long-lived effector iNKT cells from the NKT1 subset in the lungs after antigen stimulation
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-05421-w