An endogenous aryl hydrocarbon receptor ligand enhances de novo generation of regulatory T cells in humans

: The aromatic hydrocarbons receptor (AhR) is a ligand-dependent transcription factor that plays a role in mediating toxicity to xenobiotics. Its key role in immune regulation has been recently demonstrated. Recent data pointed to the efficacy of ITE (2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester), a nontoxic ligand of AhR, in experimental models of inflammatory diseases. Such effect was mainly through the expansion of regulatory T cells (Tregs). Similarly, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic ligand of AhR, has been shown to exert comparable effects on Tregs in mice. Herein, we showed that ITE has no effects on natural Tregs. However, it supports the de novo generation of Tregs in humans while promoting their suppressive functions. Our data bring new elements supporting the use of ITE in human therapy of inflammatory diseases.