Epicutaneous Tolerance Induction to a Bystander Antigen Abrogates Colitis and Ileitis in Mice

David Dunkin, M. Cecilia Berin, Lucie Mondoulet, Steven Tobar, Garabet Yeretssian, Leticia Tordesillas, Alina Iuga, Thibaut Larcher, Virginia Guillespie, Pierre Henri Benhamou, Jean Frederic Colombel, Hugh A. Sampson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: Although inflammatory bowel disease (IBD) is a failure in maintaining tolerance to the intestinal microbiota, few studies have investigated the use of immunologic tolerance as a treatment approach for IBD. We hypothesized that induction of immune tolerance at a distal site could suppress intestinal inflammation through a process of bystander regulation. Methods: Epicutaneous tolerance was induced by topical application of ovalbumin (OVA) using a Viaskin patch for 48 hours. In some experiments, a single feed of ovalbumin was used to drive epicutaneous tolerance-induced regulatory T cells (Tregs) to the intestine. The mechanism of tolerance induction was tested using neutralizing antibodies against TGF-β, IL-10, and Treg depletion using Foxp3-DTR mice. The capacity of skin-draining Tregs, or epicutaneous tolerance, to prevent or treat experimental IBD was tested using T-cell transfer colitis, dextran sodium sulfate (DSS) colitis, and ileitis in SAMP-YITFc mice. Weight loss, colonic inflammatory cytokines and histology were assessed. Results: Epicutaneous exposure to ovalbumin induced systemic immune tolerance by a TGF-β-dependent, but IL-10 and iFoxp3 + Treg-independent mechanism. Skin draining Tregs suppressed the development of colitis. Epicutaneous tolerance to a model antigen prevented intestinal inflammation in the dextran sodium sulfate and SAMP-YITFc models and importantly could halt disease in mice already experiencing weight loss in the T-cell transfer model of colitis. This was accompanied by a significant accumulation of LAP + and Foxp3 + Tregs in the colon. Conclusions: This is the first demonstration that epicutaneous tolerance to a model antigen can lead to bystander suppression of inflammation and prevention of disease progression in preclinical models of IBD.

Original languageEnglish
Pages (from-to)1972-1982
Number of pages11
JournalInflammatory Bowel Diseases
Issue number11
StatePublished - 1 Nov 2017


  • bystander suppression
  • epicutaneous tolerance
  • inflammatory bowel disease
  • regulatory T cells


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