期刊
ALLERGY
卷 72, 期 11, 页码 1686-1693出版社
WILEY
DOI: 10.1111/all.13170
关键词
Ah receptor; atopic dermatitis; Fc epsilon receptor; indoleamine 2; 3-dioxygenase; Langerhans cells
资金
- IUF - Leibniz Research Institute for Environmental Medicine
- Innate Immunity and Extrinsic Skin Aging, Dusseldorf, Germany
- Leibnizwettbewerb der Leibnizgemeinschaft [SAW-2012-IUF-1]
- Christine Kuhne - Center for Allergy Research and Education, CK-CARE
BackgroundAryl 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, Fc epsilon RI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. ObjectivesWe investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro-generated LC. MethodsEpidermal cells from healthy skin were analyzed for their expression of AhR and AhRR. LC generated from CD34(+) hematopoietic stem cells (CD34LC) 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. ResultsEpidermal LC and CD34LC express AhR and AhRR. AhR was also found in keratinocytes, which lack AhRR. AhR activation of LC by FICZ caused downregulation of Fc epsilon RI in CD34LC without affecting their maturation. AhR-mediated regulation of Fc epsilon RI did not involve any known transcription factors related to this receptor. Furthermore, we could show upregulation of IDO mediated by AhR engagement. ConclusionsOur study shows that AhR activation by FICZ reduces Fc epsilon RI and upregulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD.
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