2025/08/13 by Arno Belpaire, Annelies Demeyer, Danique Berrevoet +5 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Immune Cell Function and Interaction #T-cell and B-cell Immunology #melanin and skin pigmentation
paper · pdf · doi:10.1016/j.jid.2025.07.027
openalex publication_date 2025/08/13 · openalex created_date 2025/08/17 · openalex updated_date 2026/07/22
The kynurenine–aryl hydrocarbon receptor (AhR) axis restrains cytotoxic T-cell activity by tempering IFN-γ release and sustaining immune checkpoint expression, yet its status in vitiligo remains undefined. We profiled AhR expression in circulating T cells, quantified serum tryptophan and kynurenine, and assessed intracellular IFN-γ/IL-17A with soluble checkpoint molecules in 186 patients with nonsegmental vitiligo and 56 matched controls. Patients with vitiligo showed significantly reduced AhR expression in CD8 + T cells ( P = .003) and a higher kynurenine/tryptophan ratio in active than in stable disease ( P = .048). Low AhR expression in CD8 + T cells correlated inversely with IFN-γ–producing CD8 + cells (r = −0.376; P < .001), this correlation being stronger in active disease (r = −0.561). AhR expression positively correlated with soluble BTLA, soluble PD-1, and soluble TIM-3 levels in PBMC supernatants from patients with vitiligo. Pharmacologic activation of AhR with tapinarof dose-dependently suppressed IFN-γ + T-cell frequencies, achieving a 55% reduction at 1 μM and a 47% reduction at 3 μM compared with stimulated controls ( P < .05). These data identify disrupted kynurenine–AhR signaling as a driver of enhanced IFN-γ production in vitiligo and point to the potential of AhR agonists as targeted therapies to restore immune homeostasis and prevent disease activity in vitiligo.