BACKGROUND: Previous studies have shown that Tyk2, a member of the Janus family of protein tyrosine kinases, which are activated by a variety of cytokines, plays a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma production. On the other hand, hapten-induced contact hypersensitivity (CHS) is mediated by IFN-gamma producing CD8+ T cells and regulated by CD4+ T cells. OBJECTIVE: This study hypothesized that the CHS response might be reduced in Tyk2-deficient mice because of a lack of IFN-gamma production from CD4+ and CD8+ T cells. METHODS: The CHS reaction was evoked in wild-type and Tyk2-deficient mice and the ears of the mice were examined to measure for several cytokines. RESULTS: Ear swelling during CHS was significantly enhanced in Tyk2-deficient mice compared with the controls. IL-12 and IFN-gamma levels at the reaction sites in Tyk2-deficient mice were significantly lower than in the controls, whereas IL-2 and IL-4 levels were elevated. Furthermore, STAT3- and STAT4-phosphorylation in the draining lymph node cells of Tyk2-deficient mice decreased. CONCLUSION: These results suggest that the lack of Tyk2-mediated signal transduction enhances a compensative pathway during CHS.
BACKGROUND: Previous studies have shown that Tyk2, a member of the Janus family of protein tyrosine kinases, which are activated by a variety of cytokines, plays a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma production. On the other hand, hapten-induced contact hypersensitivity (CHS) is mediated by IFN-gamma producing CD8+ T cells and regulated by CD4+ T cells. OBJECTIVE: This study hypothesized that the CHS response might be reduced in Tyk2-deficientmice because of a lack of IFN-gamma production from CD4+ and CD8+ T cells. METHODS: The CHS reaction was evoked in wild-type and Tyk2-deficientmice and the ears of the mice were examined to measure for several cytokines. RESULTS: Ear swelling during CHS was significantly enhanced in Tyk2-deficientmice compared with the controls. IL-12 and IFN-gamma levels at the reaction sites in Tyk2-deficientmice were significantly lower than in the controls, whereas IL-2 and IL-4 levels were elevated. Furthermore, STAT3- and STAT4-phosphorylation in the draining lymph node cells of Tyk2-deficientmice decreased. CONCLUSION: These results suggest that the lack of Tyk2-mediated signal transduction enhances a compensative pathway during CHS.
Authors: Stefan F Martin; Jan C Dudda; Eva Bachtanian; Annalisa Lembo; Stefanie Liller; Christoph Dürr; Markus M Heimesaat; Stefan Bereswill; György Fejer; Ralitsa Vassileva; Thilo Jakob; Nikolaus Freudenberg; Christian C Termeer; Caroline Johner; Chris Galanos; Marina A Freudenberg Journal: J Exp Med Date: 2008-08-25 Impact factor: 14.307