Study Links Psoriasis Gene Regulation to Spatial Genome Changes
Key Takeaways
CD4+ T cells in psoriasis show altered architecture that researchers said correlates with immune gene dysregulation.
Disrupted topologically associated domains (TAD)s and loop dynamics affect expression of LYN, YBX3, and other immune genes.
Psoriasis-associated SNPs may act to modulate disease-relevant gene expression.
Results from a new study in the Journal of Investigative Dermatology showed how changes in the 3D chromatin architecture of CD4+ T cells contribute to immune dysregulation in psoriasis.
"In this study, the 3D genomic structure of CD4+ T cells from patients with psoriasis was revealed through a combined Hi-C and RNA sequencing (RNA-seq) analysis," they wrote in the study. "We then examined how spatial organization is associated with the changes in gene regulation, genetic variants, and 3D genomic reorganization in psoriasis. By integrating these modern technologies, we hope to provide deeper insights into the pathogenesis of psoriasis."
Researchers on the study performed Hi-C and RNA-sequencing on CD4+ T cells from five patients with psoriasis and three healthy controls to create a detailed 3D chromatin interaction map. Their analysis identified disruptions in topologically associated domains (TADs), altered chromatin loop dynamics, and psoriasis-associated superenhancers (SEs), which collectively drive differential gene expression linked to immune activation.
The team identified 632 differentially expressed genes in psoriasis CD4+ T cells (487 upregulated and 145 downregulated) enriched in pathways including IL-6–JAK–STAT3 signaling, TNFA/NF-κB signaling, and chemokine activity. New or disrupted TAD boundaries were reported to be associated key immunoregulatory genes. Total loop numbers were comparable between groups. Loop strength correlated with disease severity (PASI score). Changes in loop strength influenced differentially expressed genes.
An additional superenhancer analysis uncovered 376 CD4+ T cell–specific SEs, with genes such as PRKCQ-AS1 showing increased expression in psoriasis samples. Several SNPs implicated in psoriasis were located in these SE-rich regions or at disrupted loop anchors, according to the study.
“Clarifying the 3D chromatin structure in psoriasis and its role in gene regulation provides a promising avenue for the development of targeted therapies," they researchers wrote in the conclusion. "Further research is needed to determine the precise chromatin architectural changes in specific T-cell subsets in psoriasis and to translate these findings into clinical applications. With the advent of single-cell–level genomic technologies, a more nuanced understanding of the chromatin dynamics in psoriasis and other skin diseases can be expected in the near future."
Source: Qiu Yueqi, et al. J Invest Dermatol. 2025;145(4):831-841.e10. Doi:10.1016/j.jid.2024.08.006