142 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) regulates the expression of AhR-related factors(AhR, ARNT, CYP1A1), and cytokines in peripheral blood mononuclear cells and changes in differentiation of CD4+ T cells from healthy subjects, patients with atopic dermatitis and psoriasis

Abstract

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, important for xenobiotic metabolism, which binds to various endogenous and exogenous ligands in the skin. Therefore, we aim to evaluate the role of the AhR and its ligands in chronic inflammatory skin disease such as psoriasis (PS) and atopic dermatitis (AD). PS and AD patients and healthy volunteers were recruited. Blood samples were taken from three groups for isolation of peripheral blood mononuclear cells (PBMCs) and CD4+ T cell. Each isolated PBMCs and CD4+ T cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 6-for-mylindolo[3,2-b] carbasole (FICZ) under various concentrations and time duration. In PBMCs, after treatment with TCDD and FICZ, the expression of AhR-related factors and interleukin (IL)-22 were increased in PS and AD patients. IL-17 was increased in PS patients but remained stable in AD patients. In the CD4+T cells, after treatment with TCDD and FICZ, the expression of AhR-related factors and interleukin (IL)-17, IL-22 were increased in PS and AD patients. In the CD4+T cells, compared to the control group, CCR10+ cells (marker for Th22 cells) and CD161+CCR10+ cells (marker for Th17 and Th22 cells) were significantly increased in PS patients and CCR10+ cells were significantly increased in AD patients of the TCDD- treated group. In conclusion, CD4+T cells of AD and PS patients presented higher expression of AhR, CYP1A1, IL-17 and IL-22. Additionally, CD4+T cells of AD and PS patients tend to show features of Th17 cells or Th22 cells. These results suggest that AD and PS patients may be affected more sensitively to AhR ligands and activation of AhR may contribute to the disease development in AD and PS.