Janus kinase 3 (Jak3) is essential for common cytokine receptor gamma chain (gamma(c))-dependent signaling: comparative analysis of gamma(c), Jak3, and gamma(c) and Jak3 double-deficient mice

Int Immunol. 2000 Feb;12(2):123-32. doi: 10.1093/intimm/12.2.123.

Abstract

The common cytokine receptor gamma chain (gamma(c)) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby gamma(c)-deficient mice exhibit impaired T cell and B cell development. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with gamma(c), and the reported phenotypes of gamma(c)-deficient (gamma(c)(-)) and Jak3-deficient (Jak3(-)) mice are similar, indicating that Jak3 is an essential transducer of gamma(c)-dependent signals. Nevertheless, certain differences have been suggested related to the range of actions of gamma(c) and Jak3. To clarify whether gamma(c)-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in gamma(c)(-), Jak3(-), and gamma(c) and Jak3 double-deficient (gamma(c)(-)Jak3(-)) mice in the same genetic background. With the exception that T and B cells in Jak3(-) mice express high levels of gamma(c), the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among gamma(c)(-), Jak3(-) and gamma(c)(-)Jak3(-) mice. Interestingly, although Bcl-2 induction was previously suggested to be Jak3-independent, IL-7 cannot induce Bcl-2 expression in CD4 single-positive (SP) thymocytes in either gamma(c)(-) or Jak3(-) mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in gamma(c)(-) or Jak3(-) mice. These results indicate that Jak3 is absolutely essential for gamma(c)-dependent T cell and B cell development, and for gamma(c)-dependent prevention of thymocyte apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / physiology
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation
  • Flow Cytometry
  • Gene Expression Regulation
  • Genes, bcl-2
  • Intercellular Adhesion Molecule-1 / metabolism
  • Janus Kinase 3
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin-2 / metabolism
  • Signal Transduction*
  • T-Lymphocytes / physiology*
  • Transgenes

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Cytokine
  • Receptors, Interleukin-2
  • Intercellular Adhesion Molecule-1
  • Protein-Tyrosine Kinases
  • Jak3 protein, mouse
  • Janus Kinase 3