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. 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.
Zhou
Yufeng
Y
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA.
Kawasaki
Hirokazu
H
Hsu
Shih-Chang
SC
Lee
Reiko T
RT
Yao
Xu
X
Plunkett
Beverly
B
Fu
Jinrong
J
Yang
Kuender
K
Lee
Yuan C
YC
Huang
Shau-Ku
SK
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016753:Interleukin-10; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin