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.