This study demonstrates significant upregulation of Th2 and Th17/Th22 pathway-related markers in skin samples of prurigo nodularis through gene expression analysis, establishing a theoretical foundation for immune mechanism-guided therapeutic strategies.
Literature Overview
This article, titled 'Th2 mRNA gene expression analysis separates Prurigo nodularis into two immune signature groups', published in the Journal of the European Academy of Dermatology and Venereology, reviews and summarizes the immunomolecular features of prurigo nodularis and their association with disease severity. The study analyzed gene expression from skin samples of 54 patients, identifying elevated expression of IL-31 and its receptor in lesional areas, while also observing significant upregulation of OSM and OSMRβ. These findings reinforce the central role of the Th2 pathway in prurigo nodularis and provide new candidate molecules for targeted therapies.
Background Knowledge
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and cutaneous nodule formation. While existing research suggests the T helper 2 (Th2) axis is closely associated with pruritic symptoms, the molecular mechanisms of PN remain incompletely understood. This study systematically analyzed immune and barrier gene expression profiles from PN patients through the LOTUS-PN observational program, comparing them with non-lesional areas and healthy controls. Comprehensive comorbidity analyses were conducted to reveal systemic effects of PN. Although this disease shares partial immunological mechanisms with atopic dermatitis (AD), its molecular signature demonstrates distinct characteristics. Current therapeutic strategies targeting IL-31, OSM, and their receptors have shown anti-pruritic and anti-inflammatory potential in preclinical and clinical trials, making these findings instrumental for future targeted interventions.
Research Methods and Experiments
The LOTUS-PN study enrolled 54 PN patients, collecting both lesional and non-lesional skin biopsies. Histological and gene expression analyses were performed on 53 samples. The research team evaluated skin pathological features through H&E staining and immunohistochemistry, while conducting expression profiling of 46 immune and barrier-related genes using qRT-PCR. Expression data were normalized against RPLP0 and quantified as log2(expression levels). The study assessed correlations between pruritus intensity (NRS scores) and gene expression levels, employing clustering analysis to reveal interactions among different immune pathways.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides novel biomarker clues for targeted therapies in prurigo nodularis, particularly focusing on IL-31 and OSM pathways. Future research should investigate dynamic changes in gene expression and their relationships with disease progression and treatment responses. Additionally, these findings establish molecular subtyping foundations for PN, facilitating development of personalized therapeutic approaches.
Conclusion
This comprehensive gene expression analysis of prurigo nodularis patients identified significant upregulation of Th2 pathway genes (e.g., IL4R, CCL17, CCL22) and Th17/Th22 markers (e.g., IL17A, S100A7/8/9/12) in lesional skin. The study further characterized two distinct Th2 immune signatures - one co-upregulated with barrier function genes, and another associated with pro-inflammatory and immune regulatory genes. These findings enhance understanding of PN's molecular mechanisms while providing novel molecular targets for future therapies. Combined with existing biologic agent research, treatments targeting IL-31, OSM, and their receptors may play critical roles in controlling pruritus and cutaneous inflammation. Additionally, the study highlights potential cross-regulation among immune pathways in PN, offering new directions for subsequent investigations.
