Role of tyrosine kinase 2 signals during progression of psoriasis

Muromoto, Ryuta; Oritani, Kenji; Matsuda, Tadashi

Role of tyrosine kinase 2 signals during progression of psoriasis

Muromoto, Ryuta; Oritani, Kenji; Matsuda, Tadashi

Exploration of Immunology, 2022, 2022(2), 760-770

Permalink : https://hdl.handle.net/2115/87689

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アクセス権	open access
URI	https://hdl.handle.net/2115/87689
タイトル	Role of tyrosine kinase 2 signals during progression of psoriasis
著者	Muromoto, Ryuta ; Oritani, Kenji ; Matsuda, Tadashi
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
e-Rad_Researcher 70324762 著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
キーワード	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)
	psoriasis
発行日	2022-12-27
出版者	Open Exploration
収録物名	Exploration of Immunology
巻(号)	2022(2)
ページ	760-770
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
EISSN	2768-6655
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.37349/ei.2022.00081