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Epicutaneous and oral low zone tolerance protects from colitis in mice.

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Schmidt T, Lorenz N, Raker V, Reißig S, Waisman A, Weigmann B, Steinbrink K,


Schmidt T, Lorenz N, Raker V, Reißig S, Waisman A, Weigmann B, Steinbrink K, (click to view)

Schmidt T, Lorenz N, Raker V, Reißig S, Waisman A, Weigmann B, Steinbrink K,

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The Journal of investigative dermatology 2016 5 17() pii 10.1016/j.jid.2016.04.037

Abstract

Tolerance to environmental antigens which 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 TNBS-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(+) Tregs 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 form of LZT through activation of CD4(+)CD25(+)Foxp3(+) Tregs as treatment strategies for inflammatory, allergic or autoimmune diseases.

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