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. 2007 Jul 15;110(2):553-60.
doi: 10.1182/blood-2006-11-059246. Epub 2007 Mar 29.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation

Naoki Tokumasa  1 , Akira Suto, Shin-Ichiro Kagami, Shunsuke Furuta, Koichi Hirose, Norihiko Watanabe, Yasushi Saito, Kazuya Shimoda, Itsuo Iwamoto, Hiroshi Nakajima
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Free article

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation

Naoki Tokumasa et al. Blood. .
Free article

Abstract

It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper-cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2(-/-)) mice, IL-12-induced Stat4 phosphorylation was diminished in Tyk2(-/-) DCs. IL-12-induced IFN-gamma production was also significantly diminished in Tyk2(-/-) DCs to levels similar to those in Stat4(-/-) DCs. Interestingly, Tyk2(-/-) DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2(-/-) DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-gamma from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

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