FICZ, a Tryptophan photoproduct, suppresses pulmonary eosinophilia and Th2-type cytokine production in a mouse model of ovalbumin-induced allergic asthma

Most studies about functions of aryl hydrocarbon receptor (AhR) in the pathogenesis of asthma have been carried out with non-physiological industrial by-products such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene. In the present study, effects of 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct postulated as a candidate physiological ligand of AhR, on the pathogenesis of asthma were examined and then underlying mechanisms of its immumodulatory effects were investigated. FICZ significantly reduced pulmonary eosinophilia and Th2 cytokine expression in the lungs. Flow cytometric analysis of mediastinal lymph nodes showed that IL-4 producing cells decreased in FICZ-treated mice compared with PBS control. Next, effects of FICZ on in vitro Th2 differentiation and expression of the Th2 transcription factor GATA-3 were examined. CD4 + T cells were isolated from the spleen and incubated under the Th2 differentiation conditions. FICZ inhibited both Th2 differentiation and the expression of GATA-3. Finally, activation of STAT6, which is necessary for Th2 differentiation, was inhibited by FICZ.

► FICZ, a tryptophan photoproduct and an AhR ligand, reduced asthmatic symptoms.
► FICZ inhibits Th2 differentiation in vivo as well as in vitro.
► AhR inhibits activation of STAT6 and expression of GATA3.