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In vitro: Norisoboldine, dose-dependently, inhibits PMA and ionomycin-induced NFAT reporter gene expression in K562-luc cells in the range of 2-50 μM. Norisoboldine also inhibits PMA and ionomycin-induced NFAT dephosphorylation in K562-luc cells and Jurkat cells. Consequently, Norisoboldine suppresses PMA plus ionomycin-induced IL-2 expression in Jurkat cells. Norisoboldine-treated Naive CD4+CD62L+ T cells show a markedly higher frequency of Treg cells, and lead to significant up-regulation of Foxp3 expression. The expression of IL-10 is up-regulated in Norisoboldine (30 μM)-treated naive T cells as compared to the control group. Norisoboldine (30 μM) markedly decreases the levels of IL-17A and IL-17F but not IL-21 in the supernatants of naive T cells. Norisoboldine induces the differentiation of Treg cells, and the expression of CYP1A1 in lymphocytes dependent on AhR. Norisoboldine promotes AhR/Hsp90 complex disassociation and AhR nuclear translocation in lymphocytes.