1. Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1
- Author
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Kuender Yang, Beverly Plunkett, Jinrong Fu, Shau Ku Huang, Xu Yao, Yuan C. Lee, Reiko T. Lee, Yufeng Zhou, Hirokazu Kawasaki, and Shih Chang Hsu
- Subjects
Male ,C-type lectin receptor ,Receptors, Cell Surface ,Biology ,Oral tolerance ,Article ,General Biochemistry, Genetics and Molecular Biology ,Immune tolerance ,Mice ,Antigen ,Intestinal mucosa ,C-type lectin ,Food allergy ,Immune Tolerance ,medicine ,Animals ,Lectins, C-Type ,Intestinal Mucosa ,Receptor ,Anaphylaxis ,Lamina propria ,Mice, Inbred C3H ,digestive, oral, and skin physiology ,Lectin ,Serum Albumin, Bovine ,Dendritic Cells ,General Medicine ,Th1 Cells ,medicine.disease ,Interleukin-10 ,Mice, Inbred C57BL ,stomatognathic diseases ,Interleukin 10 ,Immunology ,biology.protein ,Female ,Cell Adhesion Molecules ,Food Hypersensitivity - Abstract
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.
- Published
- 2010