Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1

• Published in: Nature medicine Vol. 16; no. 10; pp. 1128 - 1133
• Main Authors: Huang, Shau-Ku, Zhou, Yufeng, Kawasaki, Hirokazu, Hsu, Shih-Chang, Lee, Reiko T, Yao, Xu, Plunkett, Beverly, Fu, Jinrong, Yang, Kuender, Lee, Yuan C
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.10.2010
• Subjects: Anaphylaxis; Anaphylaxis - immunology; Animals; Biomedical research; Cell Adhesion Molecules - immunology; Cellular biology; Dendritic cells; Dendritic Cells - immunology; Development and progression; Female; Food allergies; Food Hypersensitivity - immunology; Gastroenterology; Gene expression; Genetic aspects; Immune Tolerance; Interleukin-10 - physiology; Intestinal Mucosa - immunology; Lectins; Lectins, C-Type - immunology; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Physiological aspects; Properties; Receptors, Cell Surface - immunology; Rodents; Serum Albumin, Bovine - immunology; Th1 Cells - immunology; Taiwan
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.2201

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.