Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1
Copyright policy )Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1
We propose that a C-type lectin receptor, SIGNR-1 (also called Cd209b), helps to condition dendritic cells (DCs) in the gastrointestinal lamina propria (LPDCs) for the induction of oral tolerance in a model of food-induced anaphylaxis. Oral delivery of BSA bearing 51 molecules of mannoside (Man(51)-BSA) substantially reduced the BSA-induced anaphylactic response. Man(51)-BSA selectively targeted LPDCs that expressed SIGNR1 and induced the expression of interleukin-10 (IL-10), but not IL-6 or IL-12 p70. We found the same effects in IL-10-GFP knock-in (tiger) mice treated with Man(51)-BSA. The Man(51)-BSA-SIGNR1 axis in LPDCs, both in vitro and in vivo, promoted the generation of CD4(+) type 1 regulatory T (Tr1)-like cells that expressed IL-10 and interferon-γ (IFN-γ), in a SIGNR-1- and IL-10-dependent manner, but not of CD4(+)CD25(+)Foxp3(+) regulatory T cells. The Tr1-like cells could transfer tolerance. These results suggest that sugar-modified antigens might be used to induce oral tolerance by targeting SIGNR1 and LPDCs.
- PEKING UNION MEDICAL COLLEGE China (People's Republic of)
- JOHNS HOPKINS UNIVERSITY
- Johns Hopkins University United States
- Chang Gung University Taiwan
- Chinese Academy of Medical Sciences China (People's Republic of)
Male, Mice, Inbred C3H, Receptors, Cell Surface, Serum Albumin, Bovine, Dendritic Cells, Th1 Cells, Interleukin-10, Mice, Inbred C57BL, Mice, Immune Tolerance, DC-Specific ICAM-3 Grabbing Nonintegrin, Animals, Female, Lectins, C-Type, Intestinal Mucosa, Anaphylaxis, Cell Adhesion Molecules, Food Hypersensitivity
Male, Mice, Inbred C3H, Receptors, Cell Surface, Serum Albumin, Bovine, Dendritic Cells, Th1 Cells, Interleukin-10, Mice, Inbred C57BL, Mice, Immune Tolerance, DC-Specific ICAM-3 Grabbing Nonintegrin, Animals, Female, Lectins, C-Type, Intestinal Mucosa, Anaphylaxis, Cell Adhesion Molecules, Food Hypersensitivity
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