ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Identification of novel HIV-1 dependency factors in primary CCR4(+)CCR6(+)Th17 cells via a genome-wide transcriptional approach.Retrovirology · 2015Pooled it
- Flavonoid-modulated JAK-STAT signaling mitigates malignant transformation and drug resistance in breast tumors: A clinically relevant 3PM-guided innovation.Journal of advanced research · 2026Review
- Emerging Targets in Psoriatic Arthritis: Dual IL-17A/F and Selective TYK2 Inhibition in a Clinical Perspective.Mediterranean journal of rheumatology · 2026Review
- Ribosome biogenesis programs define a three-gene RBscore with prognostic relevance in bladder cancer.Frontiers in immunology · 2026Article
- Genetic analysis of potential biomarkers and therapeutic targets in hypoxia and pyroptosis from psoriasis.Biochemistry and biophysics reports · 2025Article
- Tyrosine kinase 2 inhibitors in the therapy of inflammatory and autoimmune diseases.Pharmacological reports : PR · 2025Review
- IL-22, a vital cytokine in autoimmune diseases.Clinical and experimental immunology · 2024Review
- Yinxie I Formula attenuates imiquimod-induced psoriasis-like skin inflammation via IL-23/IL-17 axis.Archives of dermatological research · 2024Article
- Multiplicative Effects of Essential Oils and Other Active Components on Skin Tissue and Skin Cancers.International journal of molecular sciences · 2024Review
- Pharmacokinetic Profile of Brepocitinib with Topical Administration in Atopic Dermatitis and Psoriasis Populations: Strategy to Inform Clinical Trial Design in Adult and Pediatric Populations.Pharmaceutical research · 2024Article
- TYK2 signaling promotes the development of autoreactive CD8Nature communications · 2024Article
- New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis.Pharmaceutics · 2024Review
- Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis.Journal of Taibah University Medical Sciences · 2024Article
- Excimer light effect on neurogenic inflammation in active versus stable psoriasis lesions.Lasers in medical science · 2024Article
- Article
- Tyk2 Targeting in Immune-Mediated Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Abnormal expression of interleukin-6 is associated with epidermal alternations in localized scleroderma.Clinical rheumatology · 2022Article
- The Essential Oil Derived fromMolecules (Basel, Switzerland) · 2022Article
- Gene interaction analysis of psoriasis in Chinese Han population.Molecular genetics & genomic medicine · 2022Article
- Inhibition of CtBP-Regulated Proinflammatory Gene Transcription Attenuates Psoriatic Skin Inflammation.The Journal of investigative dermatology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making JAK inhibition an appealing strategy for the treatment of psoriasis. In this study, we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose dependently (1 nM-10 μM) inhibited JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild-type mice with SAR-20347 significantly reduced IL-12-induced IFN-γ production and IL-22-dependent serum amyloid A to similar extents, indicating that, in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes and proinflammatory cytokine levels compared with both TYK2 mutant mice and wild-type controls. Taken together, these data indicate that targeting both JAK1- and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis.
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