title: Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity.
abstract: Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell-mediated inflammation with CD8+ T cells as effectors and CD4+ T cells as regulators (Treg cells) that models human allergic contact dermatitis. The integrin αE(CD103) is expressed by some T-cell and DC subsets and has been implicated in epithelial lymphocyte localization, but its role in immune regulation remains enigmatic. We have identified a function for CD103 in the development of cutaneous allergic immune responses. CHS responses, but not irritant contact dermatitis, were significantly augmented in CD103-deficient mice in hapten-challenged skin. Phenotype and function of skin DCs during sensitization were normal, whereas adoptive transfer experiments revealed that the elevated CHS response in CD103-deficient mice is transferred by primed T cells and is independent of resident cells in recipient mice. While T-cell counts were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression level of CD4+CD25+ Treg cells was significantly reduced, indicating impaired functionality. Indeed, Treg cells from CD103-deficient mice were not able to suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3+ Treg cells was involved in Treg retention to inflamed skin. These findings indicate an unexpected dichotomous functional role for CD103 on Treg cells by modulating FoxP3 expression.
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen and University of Osnabrück, Osnabrück, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Braun
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Nadin
authors.initials: N
authors.lastname: Dewert
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Fiona
authors.initials: F
authors.lastname: Brunnert
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Schnabel
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Hardenberg
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Richter
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Zachmann
authors.affiliation: Experimental Rheumatology, German Rheumatism Research Center Berlin and Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Cording
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen and University of Osnabrück, Osnabrück, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Claßen
authors.affiliation: Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen and University of Osnabrück, Osnabrück, Germany; Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Brans
authors.affiliation: Experimental Rheumatology, German Rheumatism Research Center Berlin and Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.affiliation: Experimental Rheumatology, German Rheumatism Research Center Berlin and Charité University Medicine Berlin, Campus Mitte, Berlin, Germany; Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen and University of Osnabrück, Osnabrück, Germany. Electronic address: michael.schoen@med.uni-goettingen.de.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D039001:Integrin alpha Chains / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D039001:Integrin alpha Chains; C091367:alpha E integrins; C064658:RAG-1 protein