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

Nat Med. 2010 Oct;16(10):1128-33. doi: 10.1038/nm.2201. Epub 2010 Sep 12.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphylaxis / immunology*
  • Animals
  • Cell Adhesion Molecules / immunology*
  • Dendritic Cells / immunology
  • Female
  • Food Hypersensitivity / immunology*
  • Immune Tolerance*
  • Interleukin-10 / physiology
  • Intestinal Mucosa / immunology
  • Lectins, C-Type / immunology*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Receptors, Cell Surface / immunology*
  • Serum Albumin, Bovine / immunology
  • Th1 Cells / immunology


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Interleukin-10
  • Serum Albumin, Bovine