The majority of TCDD effects are mediated via binding and activation of the intracellular aryl hydrocarbon receptor, as demonstrated by the loss of responsiveness to TCDD in AhR knockout mice. The elevated toxicity of TCDD is caused by its extremely high affinity for AhR and its long halflife. Upon ligand binding AhR undergoes a conformational change and translocates into the nucleus, where it dimerizes with the AhR nuclear translocator and regulates, by binding to xenobiotic response elements, the expression of a variety of genes, Febrifugine dihydrochloride including the xenobiotic metabolizing enzyme NDMC101 CYP1A1. In mice, AhR activation is reported to regulate T helper 17 and T regulatory cell differentiation and to modulate immune responses to experimental induced encephalomyelitis in a ligand-dependent manner. In addition, AhR has been shown to be crucial for interleukin -22 expression and a regulatory mechanism for IL-22 production via a Notch-AhR axis has been identified. We and others have demonstrated a role for AhR agonists, including TCDD, in promoting the in vitro production of IL-22 but not of IL-17 by human CD4 T cells. The possibility that in humans AhR stimulation could participate to the in vitro differentiation of IL- 10-producing Treg cells has also been suggested. IL-22 is a member of the IL-10 family of cytokines and signals via a receptor consisting of IL-22R and IL-10R2 subunits. IL-22 does not serve the communication between immune cells since cells of hematopoietic origin do not express IL-22R. It mainly acts on epithelial cells of the gastrointestinal tract and the skin, where it promotes antimicrobial defense, protection against damage and regeneration. However, its role in chronic inflammatory disorders may be either protective or highly pathogenetic. T cells able to produce IL-22 in the absence of IL-17 and interferon -c, have been named Th22 cells and are enriched in cells expressing the skin-homing chemokine receptors CCR6, CCR4 and CCR10 while lacking CXCR3. Th22 cells have been identified in the skin of individuals suffering of psoriasis and atopic dermatitis and are thought to be important in skin immunosurveillance and immunopathology.