The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a key role in linking TH17-cell-mediated autoimmunity to environmental toxins. This study shows that AhR is specifically expressed in the TH17 subset of CD4 T cells and that its activation leads to the production of the TH17 cytokine IL-22. AhR is also expressed in human TH17 cells, and activation of AhR by a high-affinity ligand during TH17 development increases the proportion of TH17 cells and their cytokine production. AhR-deficient mice can develop TH17 responses, but fail to produce IL-22 and do not show enhanced TH17 development when exposed to AhR ligands. Activation of AhR during the induction of experimental autoimmune encephalomyelitis (EAE) accelerates disease onset and increases pathology in wildtype mice, but not in AhR-deficient mice. These findings suggest that AhR ligands may act as co-factors in the development of autoimmune diseases. AhR is involved in mediating the toxicity of dioxin and other environmental toxins. It is expressed in a wide range of vertebrate cells, but its physiological role remains unclear. The study shows that AhR is expressed in the TH17 subset of CD4 T cells and that its activation leads to increased IL-22 production. IL-22 is co-expressed with IL-17 by TH17 cells and is thought to be enhanced by dendritic cell-derived IL-23. The biological functions of IL-22 are not fully understood, but it appears to be pro-inflammatory, inducing dermal inflammation and proinflammatory gene expression in the skin, while also ameliorating T cell-mediated liver injury. AhR is complexed with hsp90 in the cytoplasm until ligand binding triggers conformational changes, leading to the exchange of hsp90 for ARNT. AhR activation by FICZ, a tryptophan-derived photoproduct, upregulates genes encoding xenobiotic metabolizing cytochrome P450 enzymes such as CYP1A1. The study shows that exposure of T cells to FICZ influences the differentiation of naive CD4 T cells into effector cells, with FICZ enhancing IL-17A, IL-17F, and particularly IL-22 mRNA expression in TH17 conditions. AhR expression is only functional in CD4 T cells that have differentiated to the TH17 lineage. The study also shows that AhR is expressed in TH17 cells generated in vivo, and that its activation enhances IL-17 and IL-22 production, leading to increased autoimmune pathology. Blockade of IL-17A with an auto-vaccine or neutralizing antibody can completely prevent the development of EAE, emphasizing theThe aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a key role in linking TH17-cell-mediated autoimmunity to environmental toxins. This study shows that AhR is specifically expressed in the TH17 subset of CD4 T cells and that its activation leads to the production of the TH17 cytokine IL-22. AhR is also expressed in human TH17 cells, and activation of AhR by a high-affinity ligand during TH17 development increases the proportion of TH17 cells and their cytokine production. AhR-deficient mice can develop TH17 responses, but fail to produce IL-22 and do not show enhanced TH17 development when exposed to AhR ligands. Activation of AhR during the induction of experimental autoimmune encephalomyelitis (EAE) accelerates disease onset and increases pathology in wildtype mice, but not in AhR-deficient mice. These findings suggest that AhR ligands may act as co-factors in the development of autoimmune diseases. AhR is involved in mediating the toxicity of dioxin and other environmental toxins. It is expressed in a wide range of vertebrate cells, but its physiological role remains unclear. The study shows that AhR is expressed in the TH17 subset of CD4 T cells and that its activation leads to increased IL-22 production. IL-22 is co-expressed with IL-17 by TH17 cells and is thought to be enhanced by dendritic cell-derived IL-23. The biological functions of IL-22 are not fully understood, but it appears to be pro-inflammatory, inducing dermal inflammation and proinflammatory gene expression in the skin, while also ameliorating T cell-mediated liver injury. AhR is complexed with hsp90 in the cytoplasm until ligand binding triggers conformational changes, leading to the exchange of hsp90 for ARNT. AhR activation by FICZ, a tryptophan-derived photoproduct, upregulates genes encoding xenobiotic metabolizing cytochrome P450 enzymes such as CYP1A1. The study shows that exposure of T cells to FICZ influences the differentiation of naive CD4 T cells into effector cells, with FICZ enhancing IL-17A, IL-17F, and particularly IL-22 mRNA expression in TH17 conditions. AhR expression is only functional in CD4 T cells that have differentiated to the TH17 lineage. The study also shows that AhR is expressed in TH17 cells generated in vivo, and that its activation enhances IL-17 and IL-22 production, leading to increased autoimmune pathology. Blockade of IL-17A with an auto-vaccine or neutralizing antibody can completely prevent the development of EAE, emphasizing the