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Tyk2 is a therapeutictarget forpsoriasis-like skininflammation Masayuki IshizakiRyuta MuromotoToshihiko Akimoto2013 год

Tyk2 is a therapeutic target for psoriasis-like skin inflammation
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Аннотация: 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.
Год издания: 2013
Авторы: Masayuki Ishizaki, Ryuta Muromoto, Toshihiko Akimoto, Yuichi Sekine, Shigeyuki Kon, Manish Diwan, Hiroaki Maeda, Sumihito Togi, Kazuya Shimoda, Kenji Oritani, Tadashi Matsuda
Издательство: Oxford University Press
Источник: International Immunology
Ключевые слова: Psoriasis: Treatment and Pathogenesis, Cytokine Signaling Pathways and Interactions, T-cell and B-cell Immunology
Другие ссылки: International Immunology (HTML)
Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (PDF)
Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (HTML)
PubMed (HTML)