title: Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype in mice.
abstract: Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper-responsiveness of the skin and environmental factors. Although the important role of abnormal immune reactivity in the pathogenesis of AD is widely accepted, the role of regulatory T cells (Tregs) remains elusive. We found that the Treg population is expanded in a mouse model of AD, i.e. mice topically treated with vitamin D3 (VitD). Moreover, mice with AD-like symptoms exhibit increased inducible T-cell costimulator (ICOS)-, cytotoxic T-lymphocyte antigen-4 (CTLA-4)- and Glycoprotein-A repetitions predominant receptor (GARP)-expressing Tregs in skin-draining lymph nodes. Importantly, the differentiation of Tregs into thymus-derived Tregs is favoured in our mouse model of AD. Emigrated skin-derived dendritic cells are required for Treg induction and Langerhans cells are responsible for the biased expansion of thymus-derived Tregs . Intriguingly, thymus-derived Tregs isolated from mice with AD-like symptoms exhibit a Th2 cytokine profile. Thus, AD might favour the expansion of pathogenic Tregs able to produce Th2 cytokines and to promote the disease instead of alleviating symptoms.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Moosbrugger-Martinz
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Tripp
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmuth
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dubrac
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D058408:Th1-Th2 Balance / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; C484196:Lrrc32 protein, mouse; D008565:Membrane Proteins; D002762:Cholecalciferol
keywords: atopic dermatitis; regulatory T cells; thymic stromal lymphopoietin; vitamin D3