Abstract
Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of Gfi1-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific Gfi1-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1pos iNKT cells was significantly reduced. Furthermore, CD4pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific Gfi1-deficient mice. The α-GalCer-dependent production of IFN-γand Th2 cytokines, but not IL-17A, was severely reduced in T cell-specific Gfi1-deficient mice. In addition, a reduction of the α-GalCer-induced anti-tumor activity was observed in Gfi1-deficient mice. These findings demonstrate the important role of Gfi1 in regulating the development and function of NKT1- and NKT2-type iNKT cell subsets.
MeSH terms
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Animals
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Antigens, Ly / immunology
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CD4 Antigens / immunology
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Cell Differentiation
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Cytokines / immunology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Galactosylceramides / immunology
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Gene Deletion
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Gene Knock-In Techniques
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Interferon-gamma / immunology
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology
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Mice
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NK Cell Lectin-Like Receptor Subfamily B / immunology
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Natural Killer T-Cells / cytology
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Natural Killer T-Cells / immunology*
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Transcription Factors / genetics
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Transcription Factors / immunology*
Substances
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Antigens, Ly
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CD4 Antigens
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Cytokines
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DNA-Binding Proteins
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Galactosylceramides
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Gfi1 protein, mouse
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Klrb1c protein, mouse
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NK Cell Lectin-Like Receptor Subfamily B
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Transcription Factors
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alpha-galactosylceramide
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Interferon-gamma
Grants and funding
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Numbers 15K20149, 15K19133, 25860376, 23390075, and the Naito Foundation Natural Science Scholarship.