Notch2 and immune function

Curr Top Microbiol Immunol. 2012:360:151-61. doi: 10.1007/82_2012_235.

Abstract

Notch2 is expressed in many cell types of most lineages in the hematolymphoid compartment and has specific roles in differentiation and function of various immune cells. Notch2 is required for development of splenic marginal zone B cells and regulates differentiation of dendritic cells (DCs) in the spleen. Notch2 appears to play some specific roles in the intestinal immunity, given that the fate of mast cells and a subset of DCs is regulated by Notch2 in the intestine. Notch2 also has important roles in helper T cell divergence from naïve CD4 T cells and activation of cytotoxic T cells. Moreover, recent genetic evidence suggests that both gain-and loss-of-function abnormalities of Notch2 cause transformation of immune cells. Inactivating mutations are found in Notch2 signaling pathways in chronic myelomonocytic leukemia, while activating mutations are found in mature B cell lymphomas, which reflects the role of Notch2 in the developmental process of these cells.

Publication types

  • Review

MeSH terms

  • Cell Differentiation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology*
  • Cell Transformation, Neoplastic / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Intestines / immunology
  • Leukemia, Myelomonocytic, Chronic / genetics
  • Leukemia, Myelomonocytic, Chronic / immunology
  • Leukemia, Myelomonocytic, Chronic / metabolism
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Mast Cells / cytology
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mutation
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / immunology*
  • Receptor, Notch2 / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • NOTCH2 protein, human
  • Receptor, Notch2