Furthermore, UV exposure elicits AHR activation and the generation of FICZ, which is a high-affinity ligand for AHR activation and can further promote the differentiation of the Th17 cell population, thereby worsening the severity of lupus (Figure 2).
Bardbori et al., "Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor," Proceedings of the National Academy of Sciences of the United States of America, vol.
Mukhtar, "FICZ: a messenger of light in human skin," Journal of Investigative Dermatology, vol.
In contrast, treatment of Treg with TCDD or FICZ did not modify CpG methylation of FOXP3 over the 7-day culture, and treatment of Treg with TCDD led to an increase in CpG methylation within the IL-17A promoter at day 7 of culture (Supplemental Figure S1).
Phe Converts Treg to Th2, Whereas TCDD and FICZ Convert Treg to Th17 Cells.
However, in contrast, treatment of Treg with TCDD or FICZ induced a T cell population which expressed IL17 and ROR-y-T after 7 days of culture (Figures 4(g)4(j)).
We aimed to determine the expression of the AHR in human T helper cells and focused on the influence of different AHR ligands (FICZ, TCDD and B[a]P) on the cytokine expression under Th17 polarizing conditions.
Furthermore, the expression of AHR target genes (CYP1A1, CYP1B1, and TIPARP) was induced after stimulation with the AHR ligands FICZ, TCDD, and B[a]P (Figure 5(d)).
The AHR ligands FICZ, TCDD, and B[a]P caused a significant change in the number of cytokine producing [CD4.sup.+] T cells stimulated with anti-CD3/anti-CD28 and Th17 polarizing conditions (Figure 6(a)).
AhR activation by either FICZ or ITE inhibited the Th1 and Th17 cell polarization and induced IL-22 production by PBMCs and [CD4.sup.+]T cells.
When used, 0.05% DMSO (control), FICZ (100 nmol/L) (Enzo Life Sciences, USA), and ITE (100 nmol/L, Tocris Bioscience, USA) were added at the beginning of the culture.
AnnexinV-FITC/PI Kit (KeyGen Biotechnology, Nanjing, China) was used to evaluate the effect of FICZ and ITE on the apoptosis of PBMCs.