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Background Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells ( LC) in the epidermis of patients with atopic dermatitis ( AD) carry the high-affinity receptor for IgE, Fcε RI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. Objectives We investigated AhR and AhR repressor (Ah RR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro-generated LC. Methods Epidermal cells from healthy skin were analyzed for their expression of AhR and Ah RR. LC generated from CD34+ hematopoietic stem cells ( CD34 LC) were treated with the UV photoproduct and AhR ligand 6-formylindolo[3,2-b]carbazole ( FICZ). Cell surface receptors, transcription factors, and the tolerogenic tryptophan-degrading enzyme indoleamine 2,3-dioxygenase ( IDO) were analyzed using flow cytometry and quantitative PCR. Results Epidermal LC and CD34 LC express AhR and Ah RR. AhR was also found in keratinocytes, which lack Ah RR. AhR activation of LC by FICZ caused downregulation of Fcε RI in CD34 LC without affecting their maturation. AhR-mediated regulation of Fcε RI did not involve any known transcription factors related to this receptor. Furthermore, we could show upregulation of IDO mediated by AhR engagement. Conclusions Our study shows that AhR activation by FICZ reduces Fcε RI and upregulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD. [ABSTRACT FROM AUTHOR]