title: Cellular and molecular immunologic mechanisms in patients with atopic dermatitis.
abstract: Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.
authors: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. Electronic address: Werfel.Thomas@MH-Hannover.de.
authors: Thomas
authors: T
authors: Werfel
authors: Department of Dermatology and Allergy, Rheinische Friedrich Wilhelm University, Bonn, Germany.
authors: Jean-Pierre
authors: JP
authors: Allam
authors: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors: Tilo
authors: T
authors: Biedermann
authors: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors: Kilian
authors: K
authors: Eyerich
authors: Institute of Environmental Medicine, UNIKA-T, Technical University Munich and Helmholtz Zentrum München, Augsburg, Germany.
authors: Stefanie
authors: S
authors: Gilles
authors: Laboratory for Investigative Dermatology, Rockefeller University, and the Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Emma
authors: E
authors: Guttman-Yassky
authors: Department of Dermatology/Allergology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors: Wolfram
authors: W
authors: Hoetzenecker
authors: Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Edward
authors: E
authors: Knol
authors: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors: Hans-Uwe
authors: HU
authors: Simon
authors: Department of Dermatology and Allergy, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Andreas
authors: A
authors: Wollenberg
authors: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors: Thomas
authors: T
authors: Bieber
authors: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland.
authors: Roger
authors: R
authors: Lauener
authors: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Allergy Unit, University of Zurich, Zurich, Switzerland.
authors: Peter
authors: P
authors: Schmid-Grendelmeier
authors: Institute of Environmental Medicine, UNIKA-T, Technical University Munich and Helmholtz Zentrum München, Augsburg, Germany; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
authors: Claudia
authors: C
authors: Traidl-Hoffmann
authors: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Swiss Institute for Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors: Cezmi A
authors: CA
authors: Akdis
mesh_terms: D000367:Age Factors; D000485:Allergens / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D004781:Environmental Exposure; D000091344:Filaggrin Proteins; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D064307:Microbiota / Q000276:immunology; D011485:Protein Binding; D011537:Pruritus / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism
chemical_list: D000485:Allergens; D002352:Carrier Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E
keywords: Atopic dermatitis; IL-13; IL-31; IL-4; IgE; T(H)2; adaptive; filaggrin; innate; skin; skin barrier