The Transcriptional Repressor Gfi1 Plays a Critical Role in the Development of NKT1- and NKT2-Type iNKT Cells.
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.
Department of Obstetrics and Gynecology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.|Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Toshiaki
T
Yasuoka
Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.|Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan.|Division of Immune Regulation, Department of Proteo-Inovation, Proteo-Science Center, Ehime University, Toon, Ehime, Japan.
Makoto
M
Kuwahara
Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Takeshi
T
Yamada
Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Saho
S
Maruyama
Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan.|Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Junpei
J
Suzuki
Laboratory of Immune Regulation, RIKEN Center for Integrative Medical Sciences, 1-7-22 suehiro-cho, Tsurumi-ku, Yokohama, Japan.
Masaru
M
Taniguchi
Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Masaki
M
Yasukawa
Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.|Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan.|Division of Immune Regulation, Department of Proteo-Inovation, Proteo-Science Center, Ehime University, Toon, Ehime, Japan.
Masakatsu
M
Yamashita
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005699:Galactosylceramides / Q000276:immunology; D017353:Gene Deletion; D055879:Gene Knock-In Techniques; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
D000950:Antigens, Ly; D015704:CD4 Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D005699:Galactosylceramides; C079873:Gfi1 protein, mouse; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014157:Transcription Factors; C493154:alpha-galactosylceramide; D007371:Interferon-gamma