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Tyk2 is a therapeutic target for psoriasis-like skin inflammation
| Title: | Tyk2 is a therapeutic target for psoriasis-like skin inflammation |
| Authors: | Ishizaki, Masayuki Browse this author | | Muromoto, Ryuta Browse this author →KAKEN DB | | Akimoto, Toshihiko Browse this author | | Sekine, Yuichi Browse this author | | Kon, Shigeyuki Browse this author →KAKEN DB | | Diwan, Manish Browse this author | | Maeda, Hiroaki Browse this author | | Togi, Sumihito Browse this author | | Shimoda, Kazuya Browse this author →KAKEN DB | | Oritani, Kenji Browse this author →KAKEN DB | | Matsuda, Tadashi Browse this author →KAKEN DB |
| Keywords: | IL-17 | | IL-22 | | IL-23 | | psoriasis | | Tyk2 |
| Issue Date: | 17-Dec-2013 |
| Journal Title: | International Immunology |
| Volume: | 26 |
| Issue: | 5 |
| Start Page: | 257 |
| End Page: | 267 |
| Publisher DOI: | 10.1093/intimm/dxt062 |
| PMID: | 24345760 |
| Abstract: | Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2－/－ mice when injected with IL-23 showed significantly reduced ear skin swelling with epidermal hyperplasia and inflammatory cell infiltration compared with wild-type mice. In addition, Tyk2 deficiency reduced production of pro-inflammatory cytokines and psoriasis-relevant anti-microbial peptides. More noteworthy is that Tyk2 directly regulated IL-22-dependent inflammation and epidermal hyperplasia. Taken together with the inhibition of IL-23-induced inflammation by treatment with neutralizing antibodies against IL-17 or IL-22, Tyk2 participates in both IL-23 and IL-22 signal transduction to mediate psoriasis-like skin inflammation. On the basis of these findings, we demonstrated for the first time that a small-molecule Tyk2 inhibitor significantly inhibited IL-23-induced inflammation and cytokine production in the skin. These observations demonstrate the important role of Tyk2 in experimental skin inflammation and indicate the therapeutic potential of Tyk2 inhibition in human psoriasis. |
| Rights: | This is a pre-copy-editing, author-produced PDF of an article accepted for publication in International Immunology following peer review. The definitive publisher-authenticated version "International Immunology 2011 23(9):575-582" is available online at: http://intimm.oxfordjournals.org/content/early/2013/12/16/intimm.dxt062.long |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/57647 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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