134 Expansion of Th17 cells in CD3/CD28-activated human PBMC: Monocyte apoptosis and skin-homing T-cell bias

T-cells undergo polyclonal expansion in cutaneous psoriasis (PsC) and PsA, with persistence of “driver clones” after effective treatment (JCI 127:4031; JI 172:1935). A recent scRNA-seq study found roughly equal compartments clonal non-clonal Th17 Tc17 cells PsC (Science 371:364). We others have shown that from PBMC requires contact between monocytes memory the context TCR ligation (PNAS 104:17034; SID 139:1245). stimulated (n=153) anti-CD3/CD28 beads for 0 or 24h followed by flow cytometry (CD3+CD45RO+,CD4/CD8,CLA+/CLA-). Activation-related DEGs featured marked up-regulation signature mRNAs (IL17A, IL17F, IL22, CCL22) along Th1 cytokine IFNG, a corresponding induction IL-17A IL-22 proteins cytometry. These findings were confirmed cluster analysis libraries CD3/CD28-activated (n=4 subjects). Stratified skin homing revealed 2.9 to 12.1-fold upregulation IL17A, CCL22 CLA+ vs CLA-, without difference IFNG. IL17A IL17F overexpressed activated psoriatics vs. controls (each 1.9-fold, p=4.7x10-4). As lesional psoriatic skin, was (2.2-fold, p= 0.003) skin-homing (FUT7+) non-skin-homing (FUT7-) T-cells, whereas IFNG not. reported CITE-seq (Front Immunol 12:636720), our bulk- sc-RNA-seq experiments dramatic disappearance within CD3/CD28 activation, which imaging morphologically identified as apoptosis time-lapse microscopy. Taken together data showing IL-23 expression inflammatory monocyte-like dermal clusters (JID 141:1707), suggest contact-dependent interplay monocyte-derived clusters, maintains activation lesions