Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine

Immunity. 2011 Nov 23;35(5):780-91. doi: 10.1016/j.immuni.2011.08.013. Epub 2011 Oct 20.


Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b(+) DC subset, Notch signaling blockade ablated a distinct population marked by high expression of the adhesion molecule Esam. The Notch-dependent Esam(hi) DC subset required lymphotoxin beta receptor signaling, proliferated in situ, and facilitated CD4(+) T cell priming. The Notch-independent Esam(lo) DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b(+)CD103(+) DCs in the intestinal lamina propria and to a corresponding decrease of IL-17-producing CD4(+) T cells in the intestine. Thus, Notch2 is a common differentiation signal for T cell-priming CD11b(+) DC subsets in the spleen and intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / immunology
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Receptor, Notch2 / metabolism*
  • Signal Transduction*
  • Spleen / immunology*
  • Spleen / metabolism
  • fms-Like Tyrosine Kinase 3 / genetics


  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Rbpj protein, mouse
  • Receptor, Notch2
  • Flt3 protein, mouse
  • fms-Like Tyrosine Kinase 3

Associated data

  • GEO/GSE31551