183 Differential gene expression in psoriatic vs. normal T-cells is enhanced by CD3-CD28 activation

We performed RNA-seq on blood-derived, flow-sorted CD4 and CD8 memory T cells and myeloid dendritic cells (mDC) either directly upon isolation or after 24h of CD3-CD28 stimulation from 126 subjects (79 females, 47 males, 58 normal, 68 psoriatic), totaling 955 libraries. The filtered and aligned RNA-seq reads (>25M per sample) were analyzed by PCA, revealing clear separations on the basis of activation, CD4/CD8, gender, and skin homing (CLA), with lesser discrimination between psoriatic and healthy individuals. To focus on psoriasis-related differences, we utilized DESeq2 to identify differentially expressed genes (DEGs) as function of psoriatic phenotype in the context of CD4/CD8, T-cell activation, skin homing, and gender (FDR < 0.05, |log2 FC| > 0.585). We identified 139 psoriasis-related DEGs across all cell types, which were most significantly enriched for “IL-17 signaling pathway” (KEGG, adj. p=0.0086). Notably, IL-17 pathway genes such as IL17A, IL22, and CCL20 were more strongly induced by CD3/CD28 in CLA+ vs. CLA- T-cells (∼2-4-fold). 37 DEGs demonstrated an interaction between disease status and activation (FDR <0.05), including key immune genes IFNG, IL2RA, IFI44L, and FCGR3A. 132 psoriasis DEGs were found in CD3/CD28-stimulated CD4 T-cells vs. only 27 in resting CD4 T-cells (63 and 39, respectively, for CD8). In mDC, 276 psoriasis DEGs were most significantly enriched for “Cytokine-cytokine receptor interaction” (KEGG, adj. p=4.14x10-5). We identified 670 gender-related DEGs across all cell types. Top-ranking DEGs included Y-linked genes like TMSB4Y, and X-linked genes such as TSIX (expressed only on the inactive X in humans) and X-inactivation “escapees” including chromatin remodelers KDM6A and KDM5C. These results identify psoriasis-related, T-cell activation-enhanced DEGs in blood-derived immunocytes, highlighting the subtle but important systemic component of psoriatic immune-mediated inflammation.