AhR mediates an anti‐inflammatory feedback mechanism in human Langerhans cells involving FcεRI and IDO
Abstract
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, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes.Objectives: We 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.Methods: Epidermal 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.Results: Epidermal 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 FcεRI in CD34LC without affecting their maturation. AhR‐mediated regulation of FcεRI 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 FcεRI and upregulates IDO expression in LC. This AhR‐mediated anti‐inflammatory feedback mechanism may dampen the allergen‐induced inflammation in AD.Keywords
Funding Information
- IUF - Leibniz Research Institute for Environmental Medicine, Innate Immunity and Extrinsic Skin Aging, Düsseldorf, Germany
- Leibnizwettbewerb der Leibnizgemeinschaft (SAW-2012-IUF-1)
- Christine Kühne - Center for Allergy Research and Education, CK-CARE
This publication has 34 references indexed in Scilit:
- The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and ToxicologyPharmacological Reviews, 2015
- The Aryl Hydrocarbon Receptor: A Review of Its Role in the Physiology and Pathology of the Integument and Its Relationship to the Tryptophan MetabolismInternational Journal of Tryptophan Research, 2015
- Microbiota control of a tryptophan–AhR pathway in disease tolerance to fungiEuropean Journal of Immunology, 2014
- Gene Profiling of Narrowband UVB–Induced Skin Injury Defines Cellular and Molecular Innate Immune ResponsesJournal of Investigative Dermatology, 2013
- Influence of light on aryl hydrocarbon receptor signaling and consequences in drug metabolism, physiology and diseaseExpert Opinion on Drug Metabolism & Toxicology, 2011
- The Suggested Physiologic Aryl Hydrocarbon Receptor Activator and Cytochrome P4501 Substrate 6-Formylindolo[3,2-b]carbazole Is Present in HumansJournal of Biological Chemistry, 2009
- Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiationProceedings of the National Academy of Sciences, 2007
- The aryl hydrocarbon receptor and lightBiological Chemistry, 2006
- Ultraviolet-B Exposure of Human Skin Induces Cytochromes P450 1A1 and 1B1Journal of Investigative Dermatology, 2000
- Identification of a novel mechanism of regulation of Ah (dioxin) receptor functionGenes & Development, 1999