ArticleScientific reports2018
The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Exploring shared genetic architecture in psoriasis and rheumatoid arthritis: a multi-method approach.Journal of applied genetics · 2026Article
- Pharmacological Characterization of GLPG3667, a Tyrosine Kinase 2-Selective Inhibitor, for the Treatment of Inflammatory and Autoimmune Diseases.Inflammation · 2026Article
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Heritability and Transcriptional Impact of JAK3, STAT5A and STAT6 Variants in a Tyrolean Family.International journal of molecular sciences · 2026Article
- Tyrosine kinase 2 inhibitors in the therapy of inflammatory and autoimmune diseases.Pharmacological reports : PR · 2025Review
- Investigation of the transcriptional impact of rare germline JAK/STAT variants found in a Tyrolean alpine community.BMC genomics · 2025Article
- Characterising a Novel Therapeutic Target for Psoriasis, TYK2, Using Functional Genomics.International journal of molecular sciences · 2024Article
- Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan.Molecular medicine reports · 2024Article
- Characterization of chromatin accessibility in psoriasis.Frontiers of medicine · 2022Article
- A Scoping Review on Use of Drugs Targeting the JAK/STAT Pathway in Psoriasis.Frontiers in medicine · 2022Article
- An immunogenomic signature for molecular classification in hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2021Article
- Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspectsTurkish journal of medical sciences · 2021Review
- Type I Interferon and the Spectrum of Susceptibility to Viral Infection and Autoimmune Disease: A Shared Genomic Signature.Frontiers in immunology · 2021Review
- From Science to Success? Targeting Tyrosine Kinase 2 in Spondyloarthritis and Related Chronic Inflammatory Diseases.Frontiers in genetics · 2021Review
- Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis.Genetics and molecular biology · 2021Article
- Genetic Susceptibility of the Host in Virus-Induced Diabetes.Microorganisms · 2020Review
- TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.The Journal of clinical investigation · 2020Article
- TYK2 in Tumor Immunosurveillance.Cancers · 2020Review
- Immunology of IL-12: An update on functional activities and implications for disease.EXCLI journal · 2020Review
- Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated TYK2 in psoriasis susceptibility. We performed an in-depth association analysis of TYK2 using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the TYK2 gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be deleterious based on its location in the pseudokinase domain. We analyzed PBMCs from 29 individuals representing the haplotypes containing each of the significantly associated signals. STAT4 phosphorylation was evaluated by phospho-flow cytometry after CD3/CD28 activation of cells followed by IL-12 stimulation. Individuals carrying the protective I684S variant manifested significantly reduced p-STAT4 levels in CD4 + CD25 + CD45RO+ (mean Stimulation Index (S.I.) 48.08, n = 10) and CD8 + CD25 + CD45RO + cells (S.I. 55.71, n = 10), compared to controls homozygous for the ancestral haplotype (S.I. 68.19, n = 10 (p = 0.002) and 76.76 n = 10 (p = 0.0008) respectively). Reduced p-STAT4 levels were also observed in skin-homing, cutaneous lymphocyte associated antigen (CLA)-positive CD4 and CD8 cells from I684S carriers. No significant changes in p-STAT4 for the psoriasis-associated variant rs34536443 was found. These data establish the functional significance of the TYK2 I684S variant in psoriasis susceptibility.
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