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Role of tyrosine kinase 2 signals during progression of psoriasis

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Title: Role of tyrosine kinase 2 signals during progression of psoriasis
Authors: Muromoto, Ryuta Browse this author →KAKEN DB
Oritani, Kenji Browse this author →KAKEN DB
Matsuda, Tadashi Browse this author →KAKEN DB
Keywords: Tyrosine kinase 2 (TYK2)
interleukin-23 (IL-23)
interleukin-17 (IL-17)
T helper 1 (Th1)
T helper 17 (Th17)
signal transducer and activator of transcription 3 (STAT3)
inhibitor of nuclear factor κB kinase-ζ(IκB-ζ)
Issue Date: 27-Dec-2022
Publisher: Open Exploration
Journal Title: Exploration of Immunology
Volume: 2022
Issue: 2
Start Page: 760
End Page: 770
Publisher DOI: 10.37349/ei.2022.00081
Abstract: Psoriasis is a skin disease characterized by scaly erythema, parakeratosis, and epidermal hyperplasia. Application of imiquimod (IMQ), a ligand for Toll-like receptor 7, produces a mouse model for psoriasis. IMQ application induces scaling, erythema, and thickness in skin lesions, and the symptoms are milder in interleukin-23 p19 (Il23p19)-deficient and Il17a-deficient mice than in wild-type mice; this suggests that the interleukin-23 (IL-23)/T helper 17 (Th17) axis and Th17 cell-secreting cytokines play essential roles in the IMQ-induced psoriasis model. It is notable that a genome-wide association study identified the human tyrosine kinase 2 (TYK2) gene within the psoriasis susceptibility locus. After IMQ application, mice lacking Tyk2, a mouse homologue of the human TYK2 gene, exhibited significantly lower symptom scores of psoriasis and diminished inflammatory cell infiltration in the skin lesions. Tyk2-deficient mice also failed to increase CD4+IL-17+ or CD4+ interferon-γ+ (IFN-γ+) T cells in the draining lymph nodes or to produce Th17 cell-related cytokines after IMQ application. Furthermore, Tyk2 deficiency led to diminished skin inflammation induced by IL-23 and IL-22 injections. These results indicate that Tyk2-mediated signals in mice contribute to multiple steps of immune and inflammatory responses during the development of psoriasis; therefore, TYK2 targeting may be a promising strategy to treat patients with psoriasis. Recent clinical trials have shown that TYK2 inhibitors have a high overall response rate with good tolerability in the management of psoriasis. This review describes the fundamental mechanisms of Tyk2 inhibition in immune/inflammatory diseases.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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