Lunatic fringe controls T cell differentiation through modulating notch signaling

J Immunol. 2006 Dec 15;177(12):8365-71. doi: 10.4049/jimmunol.177.12.8365.


T cells differentiate from bone marrow-derived stem cells by expressing developmental stage-specific genes. We here searched arrays of genes that are highly expressed in mature CD4-CD8+ (CD8 single-positive (SP)) T cells but little in CD4+CD8+ (double-positive (DP)) cells by cDNA subtraction. Lunatic fringe (Lfng), a modulator of Notch signaling, was identified to be little expressed in DP cells and highly expressed in CD8SP T cell as well as in CD4-CD8- (double-negative (DN)) and mature CD4+CD8- (CD4SP) T cells. Thus, we examined whether such change of expression of Lfng plays a role in T cell development. We found that overexpression of Lfng in Jurkat T cells strengthened Notch signaling by reporter gene assay, indicating that Lfng is a positive regulator for Notch signaling in T cells. The enforced expression of Lfng in thymocytes enhanced the development of immature CD8SP cells but decreased mature CD4SP and CD8SP cells. In contrast, the down-regulation of Lfng in thymocytes suppressed DP cells development due to the defective transition from CD44+CD25- stage to subsequent stage in DN cells. The overexpression of Lfng in fetal liver-derived hemopoietic stem cells enhanced T cell development, whereas its down-regulation suppressed it. These results suggested that the physiological high expression of Lfng in DN cells contributes to enhance T cell differentiation through strengthening Notch signaling. Shutting down the expression of Lfng in DP cells may have a physiological role in promoting DP cells differentiation toward mature SP cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens
  • CD8 Antigens
  • Cell Differentiation*
  • Gene Expression Regulation
  • Glycosyltransferases / physiology*
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Notch / metabolism*
  • Signal Transduction / physiology*
  • T-Lymphocytes / cytology*
  • Thymus Gland / cytology


  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Notch
  • Glycosyltransferases
  • Lfng protein, mouse