[摘要]：BACKGROUND & AIMS: Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen-related inflammation in the gastrointestinal tract. Interferon (IFN)-lambda regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-lambda in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell-mediated inflammation in the intestine. METHODS: Expression of IFN-lambda and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell-mediated intestinal inflammation was used to examine the role of IFN-lambda and T cells in oral tolerance in the intestine. RESULTS: CD3(+) cells expressed the IFN-lambda receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-lambda and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-lambda-primed CD3(+) cells inhibited Th2 cell-mediated inflammation in the intestine. CONCLUSIONS: IFN-lambda is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell-mediated inflammation in patients.
