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Blood, 15 July 2007, Vol. 110, No. 2, pp. 553-560.
Prepublished online as a Blood First Edition Paper on March 29, 2007; DOI 10.1182/blood-2006-11-059246.


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Submitted November 22, 2006
Accepted March 26, 2007

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, Akira Suto, Shin-ichiro Kagami, Shunsuke Furuta, Koichi Hirose, Norihiko Watanabe, Yasushi Saito, Kazuya Shimoda, Itsuo Iwamoto, and Hiroshi Nakajima*

Department of Allergy and Clinical Immunology, Clinical Cell Biology, Chiba University, Chiba, Japan
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan
Gastroenterogy and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba, Japan

* Corresponding author; email: nakajimh{at}faculty.chiba-u.jp.

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 the similar levels 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 for the induction of Th1 cell differentiation but not of 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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