3.1 A distinct cluster of CD4+ T cells dictates therapeutic response to psoriasis patients to treatment with UVB
Peripheral blood mononuclear cells (PBMCs) were isolated from 38 blood samples taken from 19 mild to severe psoriasis patients (Table S1) before and after phototherapy at the Department of Dermatology, National Taiwan University Hospital (NCT05636839) and analyzed using cytometry by time of flight (CyTOF). A total of 42 markers targeting surface molecules and transcription factors were measured. FlowSOM analysis identified distinct immune cell clusters within the PBMC population (Figure S1). We identified a cluster (cluster 11) of CD4+ T cells characterized by high expression of CD25, FOXP3, and low expression of CD127 (Figure 1A), which exhibited elevated levels of TIGIT, CTLA4, TIM3, CD39, and Helios, markers associated with regulatory T cell (Treg) activation (Figure 1B). Receiver operating characteristic (ROC) curves were applied to assess the discriminative ability for UVB response. A total of 7 responders out of the 19 recruited patients achieved an over 50% reduction in Psoriasis Area Severity Index (PASI) score. The area under the curve (AUC) for cluster 11 at baseline showed a significant prediction for therapeutic response in psoriasis (adjusted-AUC, 0.85; 95% confidence interval (CI), 0.65 to 1.00) (Figure 1C). We also found that UVB significantly increased the size of cluster 11, but not the other clusters (Figure 1D and Figure S2). This specific cluster was recapitulated using conventional manual gating on HLADR and TIGIT pre- and post-UVB treatment (P = 0.03, Figure 1E, upper) or HLADR and TIM3 (P = 0.04, Figure 1E lower), indicating the TCR activation phenotype of Tregs after UVB treatment. Our results suggest that UVB induces activated Tregs in an inflammatory context.