Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, The University of Manchester, Manchester M13 9PT, UK.
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester M13 9PT, UK.
Biomolecules. 2024 May 3;14(5):548. doi: 10.3390/biom14050548.
Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world's population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with Genome-Wide Association (GWAS) studies showing that many psoriasis risk genes lie along the IL-23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. This review is focused on the IL-23/Th17 axis, providing an insight into key cell types, cytokines, and intracellular signaling pathways involved. This includes examination of currently available biological treatments, time to relapse post drug withdrawal, and rates of primary/secondary drug failure, showing the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely to reduce the burden of disease for the longest period possible.
银屑病是一种终身性、系统性、免疫介导的炎症性皮肤病,影响全球 1%-3%的人口,其对生活质量的影响与癌症或糖尿病等疾病相当。遗传是银屑病的单一最大风险因素,全基因组关联 (GWAS) 研究表明,许多银屑病风险基因位于 IL-23/Th17 轴上。通过 GWAS 确定的潜在银屑病风险基因可以使用功能基因组学进行注释和表征,从而确定新的药物靶点并重新利用现有药物。本综述重点介绍了 IL-23/Th17 轴,深入探讨了涉及的关键细胞类型、细胞因子和细胞内信号通路。这包括检查目前可用的生物治疗方法、停药后复发的时间以及原发性/继发性药物失败的比率,表明需要更深入地了解银屑病的潜在遗传机制以及它们如何影响治疗。这可能使患者能够根据最有可能在最长时间内减轻疾病负担的治疗方法进行分层。