Psoriasis is a common chronic skin disease that causes a rash on affected individuals, characterised by itchy, scaly patches.1 Currently, there is no cure for this disease that affects 2-3% of the worldwide population.2 Instead, treatment options are focused on management and control rather than healing or eradication. Individuals affected by psoriasis have a few options available to them: topical, systemic and phototherapy, in an attempt to mitigate their symptoms. The severity of their disease dictates the therapies used in retaliation, starting with topicals for mild symptoms, and moving onto systemic medicine therapy for more severe cases of psoriasis. While biologics have targeted the IL-17 pathway and revolutionised treatment for psoriasis, as with many conditions, not every patient reacts favourably to treatments. Identifying additional drug targets and biomarkers could enhance treatment efficacy and personalisation.3
The IL-17 Pathway and its Significance in Psoriasis
The IL-17 signaling pathway plays a central role in driving inflammation in psoriasis, making it a major target for therapeutic intervention.4 Currently, three biologic drugs—ixekizumab, secukinumab, and brodalumab—have been approved by the FDA to treat moderate to severe plaque psoriasis by targeting this pathway. Ongoing research is also exploring the effectiveness of two newer biologics: bimekizumab, which blocks both IL-17A and IL-17F, and netakimab, which targets IL-17A specifically. Yet, variability in patient response underscores the need for deeper insights into the IL-17 signaling cascade.5
Discovery of Novel IL-17 Related Genes
A recent study by He et al. aimed to uncover new genes associated with the IL-17 signaling pathway that could serve as biomarkers or therapeutic targets for psoriasis. Recognising that while the Th17/IL-17A axis is known to play a critical role in psoriasis pathogenesis, many upstream regulatory genes remain unidentified, and the researchers sought to fill this knowledge gap. To achieve this, they employed machine learning algorithms and bioinformatics analyses on multiple gene expression datasets from psoriasis patients and healthy controls. This approach led to the identification of three genes – CCR7, IL2RG AND PLEK – which were found to be upregulated in psoriatic lesions and closely associated with the Th17/IL-17A pathway. CCR7 is involved in T-cell migration, which is upregulated in psoriatic lesions. IL2RG is a component of multiple interleukin receptors; its expression correlates with the severity of the disease, and PLEK was previously unassociated with psoriasis, but its inhibition reduces IL-17A-mediated inflammation. Gene expression was confirmed in patient samples and mouse models, highlighting their potential as therapeutic targets. These findings suggest that CCR7, ILR2G and particularly PLEK could serve as novel prognostic and therapeutic biomarkers for psoriasis, offering potential avenues for more targeted and effective treatments.6
Implications for Drug Discovery
The discovery of CCR7, IL2RG, and PLEK as novel genes linked to the IL-17 pathway presents exciting new opportunities for advancing psoriasis treatment. These targets offer potential for therapies that go beyond the current IL-17 inhibitors, broadening the landscape of immune modulation in chronic skin inflammation. With strong associations to IL-17-driven inflammation, CCR7, IL2RG, and PLEK have emerged as promising candidates for therapeutic intervention.7 Their elevated expression in psoriatic lesions and connection to Th17 signaling make them ideal targets for next-generation treatments.
Innovative approaches are now possible for drug development strategies, highlighting small molecule inhibitors, which are custom-designed compounds that can be developed to regulate the activity of these newly identified genes, potentially offering oral or topical options for patients.8 Additionally, monoclonal antibodies targeting CCR7, IL2RG, or PLEK may offer a more specific and durable immune response with fewer off-target effects compared to broader immunosuppressants.
To evaluate these new therapeutic strategies, researchers can leverage advanced preclinical systems such as human skin explants and organotypic cultures. These models closely mimic human skin biology, enabling early insights into drug efficacy and safety in a physiologically relevant context. As research progresses, these findings could pave the way for more personalised and effective treatments for individuals living with moderate to severe psoriasis.
Identification of hub genes from WCGNA and differentially expressed genes. (A-C) GSEA of Th17 cell differentiation, Th17 cell immune response, and the IL-17A signaling pathway in psoriasis and NHD’ tissues.9
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The identification of CCR7, IL2RG, and PLEK as genes associated with the IL-17 pathway deepens our understanding of psoriasis pathogenesis. While these genes are consistently upregulated in psoriatic lesions across patient datasets, the study does not provide direct evidence of variability between individuals—an essential feature for establishing true precision medicine applications. However, their involvement in the broader inflammatory network suggests they could complement existing biomarker panels and contribute to a more refined molecular “fingerprint” of the disease. This expanded biomarker repertoire could support more targeted research efforts and, potentially, the development of tailored therapeutic approaches as further patient-specific data becomes available.10
Although CCR7, IL2RG, and PLEK show promise as biomarkers, their role in stratifying patients or predicting treatment response has not yet been validated. For now, they offer additional insight into the molecular mechanisms underpinning psoriasis and may serve as a foundation for future studies exploring their relevance in personalised treatment planning. Integrating omics technologies—genomics, transcriptomics, and proteomics—will be critical in this next phase of research, helping to determine whether these markers offer meaningful precision medicine advantages over existing options.
As precision medicine evolves, the integration of multi-omics data and emerging biomarkers like CCR7, IL2RG, and PLEK may eventually transform how chronic inflammatory skin diseases such as psoriasis are diagnosed and managed—but more work is needed to establish their clinical utility on an individual level.
Conclusion
The discovery of IL-17 related genes, CCR7, IL2RG, and PLEK, represents a promising advancement in the journey toward more personalised and effective treatments for psoriasis. By bridging cutting-edge research with clinical application, these findings lay the groundwork for targeted therapies and precision diagnostics that address the unique biological profile of each patient. Moving forward, sustained collaboration between researchers and clinicians will be key to unlocking the full potential of these biomarkers and transforming them into real world solutions for individuals living with psoriasis.
References
1. https://www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840
2. Drakos, A., & Vender, R. (2022). A Review of the Clinical Trial Landscape in Psoriasis: An Update for Clinicians. Dermatology and therapy, 12(12), 2715–2730. https://doi.org/10.1007/s13555-022-00840-9
3. https://www.nhs.uk/conditions/psoriasis/treatment/
4. Mosca, M., Hong, J., Hadeler, E., Hakimi, M., Liao, W., & Bhutani, T. (2021). The Role of IL-17 Cytokines in Psoriasis. ImmunoTargets and therapy, 10, 409–418. https://doi.org/10.2147/ITT.S240891
5. Blauvelt, A., & Chiricozzi, A. (2018). The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis. Clinical reviews in allergy & immunology, 55(3), 379–390. https://doi.org/10.1007/s12016-018-8702-3
6. He, X., Huang, J., Ma, H. et al. Identification of novel IL17-related genes as prognostic and therapeutic biomarkers of psoriasis using comprehensive bioinformatics analysis and machine learning. Sci Rep 15, 11295 (2025). https://doi.org/10.1038/s41598-025-87556-w
7. Van Raemdonck K, Umar S, Palasiewicz K, Volkov S, Volin MV, Arami S, Chang HJ, Zanotti B, Sweiss N, Shahrara S. CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis. Cell Mol Life Sci. 2020 Apr;77(7):1387-1399. doi: 10.1007/s00018-019-03235-w. Epub 2019 Jul 24. PMID: 31342120; PMCID: PMC10040247.
8. Premalatha, Akarapu & Manisha, Dr & Bora, Atul & Bhoomandla, Srinu & Aruna, Dr & Nakkella, Kumari. (2023). Recent Advances in Drug Discovery: Innovative Approaches and Targeted Therapeutics. European Chemical Bulletin. 2068.
9. He, X., Huang, J., Ma, H. et al. Identification of novel IL17-related genes as prognostic and therapeutic biomarkers of psoriasis using comprehensive bioinformatics analysis and machine learning. Sci Rep 15, 11295 (2025). https://doi.org/10.1038/s41598-025-87556-w
10. Premalatha, Akarapu & Manisha, Dr & Bora, Atul & Bhoomandla, Srinu & Aruna, Dr & Nakkella, Kumari. (2023). Recent Advances in Drug Discovery: Innovative Approaches and Targeted Therapeutics. European Chemical Bulletin. 2068.
