The Transcriptional Repressor Gfi1 Plays a Critical Role in the Development of NKT1- and NKT2-Type iNKT Cells

PLoS One. 2016 Jun 10;11(6):e0157395. doi: 10.1371/journal.pone.0157395. eCollection 2016.

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

  • Animals
  • Antigens, Ly / immunology
  • CD4 Antigens / immunology
  • Cell Differentiation
  • Cytokines / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Galactosylceramides / immunology
  • Gene Deletion
  • Gene Knock-In Techniques
  • Interferon-gamma / immunology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily B / immunology
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*

Substances

  • Antigens, Ly
  • CD4 Antigens
  • Cytokines
  • DNA-Binding Proteins
  • Galactosylceramides
  • Gfi1 protein, mouse
  • Klrb1c protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily B
  • Transcription Factors
  • alpha-galactosylceramide
  • Interferon-gamma

Grant support

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.