title: Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis-like symptoms in mice.
abstract: Atopic dermatitis (AD) is a chronic inflammatory disease controlled by the innate and adaptive immune system. To elucidate the impact of innate immune signaling in AD, we analyzed MyD88-deficient mice in a murine model of AD-like dermatitis by epicutaneous sensitization with ovalbumin (OVA). Global MyD88 deficiency led to reduced epidermal thickening and diminished accumulation of macrophages within the inflamed skin. In addition, we observed impaired emigration of Langerhans cells (LCs) out of the epidermis of MyD88-deficient mice. These findings indicate that MyD88 deficiency affects various skin-resident cell types in the AD model. Moreover, production of IFN-g, IL-17, and CCL17 was reduced in skin draining lymph node cells and OVA-specific immunoglobulin levels were lower in MyD88-deficient mice. We further investigated the role of MyD88 in keratinocytes, as keratinocytes contribute to AD pathology. Exclusive expression of MyD88 in epidermal keratinocytes partially restored LC emigration after AD induction and expression of CCL17 in skin draining lymph nodes (LNs), but did not promote epidermal thickening nor production of IL-17. Altogether, these data demonstrate that MyD88 signaling in keratinocytes is able to restore LC migration in an otherwise MyD88-deficient background, and significantly contributes to the development of AD-like dermatitis.
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.|IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Didovic
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.|IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Friederike V
authors.initials: FV
authors.lastname: Opitz
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.|IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D002465:Cell Movement / Q000235:genetics; D054414:Chemokine CCL17 / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000473:pathology
chemical_list: D000906:Antibodies; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; C098680:Il17a protein, mouse; D020381:Interleukin-17; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Allergology; Dermatitis; Innate immunity; Langerhans cells; MyD88 signaling; Skin inflammation