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

Open Access
Publisher Website
Google Scholar
Abstract
The common cytokine receptor γ chain (γc) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby γc-deficient mice exhibit impaired T cell and B cell development. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with γc, and the reported phenotypes of γc-deficient (γc–) and Jak3-deficient (Jak3–) mice are similar, indicating that Jak3 is an essential transducer of γc-dependent signals. Nevertheless, certain differences have been suggested related to the range of actions of γc and Jak3. To clarify whether γc-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in γc–, Jak3–, and γc and Jak3 double-deficient (γc–Jak3–) mice in the same genetic background. With the exception that T and B cells in Jak3– mice express high levels of γc, the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among γc–, Jak3– and γc–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 γc– or Jak3– mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in γc– or Jak3– mice. These results indicate that Jak3 is absolutely essential for γc-dependent T cell and B cell development, and for γc-dependent prevention of thymocyte apoptosis.