title: Interferon-λ mediates oral tolerance and inhibits antigen-specific, T-helper 2 cell-mediated inflammation in mouse intestine.
abstract: OBJECTIVE
  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)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ 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-λ 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-λ and T cells in oral tolerance in the intestine.
  
  
  RESULTS
  CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ 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-λ-primed CD3+ cells inhibited Th2 cell-mediated inflammation in the intestine.
  
  
  CONCLUSIONS
  IFN-λ 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.
authors.affiliation: Clinical Experimental Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China. shoahenghe@hotmail.com
authors.forename: Shao-Heng
authors.initials: SH
authors.lastname: He
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Song
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Lin-Fu
authors.initials: LF
authors.lastname: Zhou
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Ma
authors.forename: Lei-Di
authors.initials: LD
authors.lastname: Zhao
authors.forename: Tong-Li
authors.initials: TL
authors.lastname: Li
authors.forename: Shang-Guo
authors.initials: SG
authors.lastname: Tang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004751:Enteritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005434:Flow Cytometry; D019672:Genes, T-Cell Receptor; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000276:immunology*; D010047:Ovalbumin; D010587:Phagocytosis; D018121:Receptors, Cytokine / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D010047:Ovalbumin; D018121:Receptors, Cytokine; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda