Epicutaneous and Oral Low-Zone Tolerance Protects from Colitis in Mice

被引:5
作者
Schmidt, Talkea [1 ]
Lorenz, Nadine [1 ]
Raker, Verena [1 ]
Reissig, Sonja [2 ]
Waisman, Ari [2 ]
Weigmann, Benno [3 ]
Steinbrink, Kerstin [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany
[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, D-55131 Mainz, Germany
[3] Univ Erlangen Nurnberg, Dept Gastroenterol, Erlangen, Germany
关键词
REGULATORY T-CELLS; ALLERGIC CONTACT-DERMATITIS; PLASMACYTOID DENDRITIC CELLS; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL INFLAMMATION; SKIN INFLAMMATION; IMMUNE-RESPONSE; ICOS CONTROLS; MOUSE MODELS; TGF-BETA;
D O I
10.1016/j.jid.2016.04.037
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:1831 / 1839
页数:9
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