C-type lectin SIGNR1-mediated oral tolerance to food systemic anaphylaxis

We propose that a C-type lectin receptor, SIGNR-1, plays a role in conditioning gastrointestinal lamina propria (LP) DC subset for the induction of oral tolerance in a model of food-induced anaphylaxis. Oral delivery of bovine serum albumin (BSA) bearing 51 mols of mannosides (Man(51)-BSA) significantly reduced the levels of BSA-induced anaphylactic response. Man(51)-BSA was found to, selectively, target the LPDC subset expressing a member of the CLRs, SIGNR1, and induce the expression of IL-10, but not IL-6 and IL-12p70. This was noted also in Man(51)-BSA-treated IL-10-GFPknockin (tiger) mice. The Man(51)-BSA–SIGNR1 axis in LPDCs, both in vitro and in vivo, promoted the generation of CD4(+) Tr1-like cells expressing IL-10 and IFN-γ, in a SIGNR-1- and IL-10-dependent manner, but not of CD4(+)CD25(+)Foxp3(+) Tregs. The in vivo-generated Tr1-like cells were capable of transferring tolerance. These results suggest the potential utility of sugar-modified antigen in oral tolerance through targeting of SIGNR1 and LPDCs.