title: Epicutaneous and Oral Low-Zone Tolerance Protects from Colitis in Mice.
abstract: Tolerance to environmental antigens that encounter the organism at interfaces like skin or gut prevents deleterious systemic immune responses. The aim of this study was to analyze whether and how low doses of haptens, by entry through the skin or gastrointestinal tract, affect the outcome of the predominantly Th1/Th17-mediated 2,4,6-trinitro-benzenesulfonic acid-induced colitis, which mimics an autoimmune bowl disease in man. Epicutaneous and oral applications of low doses of the allergen resulted in the induction of low-zone tolerance (LZT) and protected from colitis development, demonstrated by a significantly reduced inflammatory response of the gut in vivo. In line with this observation, we found a significantly diminished Th1/Th17-mediated T cell response and reduced T cell proliferation after both tolerance regimes, indicating that epicutaneous LZT is just as well efficient as oral tolerance in prevention of a gut-associated inflammatory immune response. Use of a second, unrelated hapten for LZT induction revealed an antigen-specific tolerance mechanism. Intriguingly, in the absence of hapten-activated CD4(+)CD25(+)Foxp3(+) regulatory T cells and IL-10, epicutaneous and oral LZT failed to abrogate the development of the intestinal inflammation. In conclusion, this study highlights in particular epicutaneous immunotherapies in the form of LZT through activation of CD4(+)CD25(+)Foxp3(+) regulatory T cells as treatment strategies for inflammatory, allergic, or autoimmune diseases.
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Talkea
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lorenz
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Raker
authors.affiliation: Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Reißig
authors.affiliation: Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Department of Gastroenterology, University of Erlangen, Erlangen, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany. Electronic address: kerstin.steinbrink@unimedizin-mainz.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinbrink
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000517:prevention & control*; D003877:Dermatitis, Contact / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000485:Allergens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10