Background:
Inflammatory bowel disease (IBD) involves an increase in T effector cells in the intestines that disrupts the normal balance with T regulatory cells (Tregs). A
therapy that restores this balance has the potential to treat IBD. We have shown that epicutaneous exposure to OVA induces Tregs that are able to induce tolerance. The Tregs also migrate to the intestines where they alleviate
colitis in mice, demonstrating the potential for skin induced Tregs to treat intestinal
inflammation. We investigated the role of Foxp3,
IL-10, and TGF-β in the suppression of
colitis by epicutaneous
immunotherapy (ET). Methods: RAG1-/- mice were transferred with CD4+CD45RBhi T cells from wild type mice to induce
colitis. To determine whether Foxp3+ Tregs, IL-10-, or TGF-β-producing Tregs were necessary, Foxp3-DTR, IL-10-/-, or CD4-dnTGFBRII mice were immunized with OVA and OVA TCR enriched T cells were added. As control groups, some mice were given OVA TCR enriched T cells from wild type mice or no OVA TCR enriched T cells. Half of the mice in each group were then exposed on the skin to Viaskin patches containing OVA weekly for 3 weeks. Mice given OVA TCR enriched T cells from Foxp3-DTR mice were given
diphtheria toxin (DT) or not in addition to ET. Mice were assessed for
weight loss, colon length, colonic
cytokine production, and histological
inflammation. Results: ET, after injection with OVA TCR enriched T cells derived from wild type mice, prevented
weight loss, decreased colonic inflammatory
cytokine production and histological
colitis. ET in the absence of the OVA TCR enriched T cells did not alleviate
colitis. ET, after injection with OVA TCR enriched T cells derived from Foxp3-DTR mice, prevented
weight loss, decreased colonic inflammatory
cytokine production, and histological
colitis. Ablation with DT did not impair the ability of ET to alleviate
colitis. ET failed to alleviate
colitis when OVA TCR enriched T cells were derived from IL-10-/- or CD4-dnTGFBRII mice. Conclusions: ET through induction of Tregs, which produce
IL-10 and TGF-β, could be a promising treatment for IBD.