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. Man₅₁-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 3 (IFN-γ 3), 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.