PD-1 Engagement and Circulating Th17 Effector Activity During Secukinumab Treatment in Plaque Psoriasis

INTRODUCTION: Plaque psoriasis (PP) is a chronic immune-mediated inflammatory disease driven by dysregulation of the IL-23/Th17/IL-17 axis. Although IL-17A targeted biologics achieve robust clinical efficacy, how cytokine blockade is accompanied by systemic immune remodeling during disease control remains incompletely understood. The objective was to characterize changes in circulating T-cell subsets associated with clinical response to IL-17A blockade and to examine the relationship between PD-1 engagement and Th17 effector activity. METHODS: Longitudinal immune profiling was performed in seven patients with PP before and after achieving a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) following secukinumab treatment. Circulating T-cell subsets, PD-1 expressing populations, and cutaneous lymphocyte antigen positive (CLA+) T cells were quantified by flow cytometry, with plasma cytokine profiling. Ex vivo T-cell responses to the PD-1 agonist peresolimab were assessed in an independent cohort. RESULTS: At baseline, patients exhibited reduced frequencies of regulatory T cells compared with healthy controls. Following PASI 90, circulating Th17 and Th2 cell frequencies increased despite minimal sustained changes in plasma cytokines, indicating dissociation between effector T-cell expansion and soluble mediators during IL-17A blockade. Circulating CD4+CLA+T cells were partially restored. Treatment was accompanied by increased frequencies of PD-1 expressing CD4+T-cell subsets, which showed an inverse association with disease activity over time. Ex vivo PD-1 engagement selectively reduced IL-17A producing CD4+ T cells, with limited effects on IFN-γ. CONCLUSIONS: PD-1 likely restrains Th17 activity during IL-17A blockade, a hypothesis that warrants validation in larger cohorts. Successful therapy in PP appears to reflect immune reorganization through PD-1/Th17 interactions, rather than systemic suppression.