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T Cells1
* Division of Host Defense,
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; and
Department of Internal Medicine, Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan
Tyrosine kinase 2 (Tyk2), a member of the JAK-signal transducer family, is involved in intracellular signaling triggered by various cytokines, including IL-23. We have recently reported that resident 
T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23. In this study, we examined importance of Tyk2-mediated signaling in the IL-17 production by T cells using Tyk2 deficient (–/–) mice. T cells in the peritoneal cavity of Tyk2–/– mice displayed effecter/memory phenotypes and TCR V repertoire similar to those in Tyk2+/+ mice and produced comparable level of IL-17 to those in Tyk2+/+ mice in response to PMA and ionomycin, indicating normal differentiation to IL-17-producing effectors in the absence of Tyk2-signaling. However, T cells in Tyk2–/– mice produced less amount of IL-17 in response to IL-23 in vitro than those in Tyk2+/+ mice. Similarly, T cells in the peritoneal cavity of Tyk2–/– mice showed severely impaired IL-17 production after an i.p. infection with E. coli despite comparable level of IL-23 production to Tyk2+/+ mice. As a consequence, Tyk2–/– mice showed a reduced infiltration of neutrophils and severely impaired bacterial clearance after Escherichia coli infection. These results indicate that Tyk2-signaling is critical for IL-23-induced IL-17 production by T cells, which is involved in the first line of host defense by controlling neutrophil-mediated immune responses.
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1 This work is partly supported by Grant-in Aid for Scientific Research on Priority Areas, Japan Society for the Promotion of Science.
2 Address correspondence and reprint requests to Dr. Yasunobu Yoshikai, Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. E-mail address: yoshikai{at}bioreg.kyushu-u.ac.jp
3 Abbreviations used in this paper: Tyk2, tyrosine kinase 2; PEC, peritoneal exudate cell; LPL, lamina propria lymphocyte; IEL, intraepithelial lymphocyte.
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