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

Yufeng Zhou, Hirokazu Kawasaki, Shih Chang Hsu, Reiko T. Lee, Xu Yao, Beverly Plunkett, Jinrong Fu, Kuender Yang, Yuan C. Lee, Shau Ku Huang

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1128-1133
Number of pages6
JournalNature Medicine
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 1 2010
Externally publishedYes

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C-Type Lectins
Anaphylaxis
Interleukin-10
Regulatory T-Lymphocytes
Food
Bearings (structural)
Mannosides
Tigers
T-cells
Interleukin-12
Sugars
Dendritic Cells
Interferons
Interleukin-6
Mucous Membrane
Antigens
Molecules
mannose-bovine serum albumin conjugate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. / Zhou, Yufeng; Kawasaki, Hirokazu; Hsu, Shih Chang; Lee, Reiko T.; Yao, Xu; Plunkett, Beverly; Fu, Jinrong; Yang, Kuender; Lee, Yuan C.; Huang, Shau Ku.

In: Nature Medicine, Vol. 16, No. 10, 01.10.2010, p. 1128-1133.

Research output: Contribution to journalArticle

Zhou, Y, Kawasaki, H, Hsu, SC, Lee, RT, Yao, X, Plunkett, B, Fu, J, Yang, K, Lee, YC & Huang, SK 2010, 'Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1', Nature Medicine, vol. 16, no. 10, pp. 1128-1133. https://doi.org/10.1038/nm.2201
Zhou Y, Kawasaki H, Hsu SC, Lee RT, Yao X, Plunkett B et al. Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. Nature Medicine. 2010 Oct 1;16(10):1128-1133. https://doi.org/10.1038/nm.2201
Zhou, Yufeng ; Kawasaki, Hirokazu ; Hsu, Shih Chang ; Lee, Reiko T. ; Yao, Xu ; Plunkett, Beverly ; Fu, Jinrong ; Yang, Kuender ; Lee, Yuan C. ; Huang, Shau Ku. / Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. In: Nature Medicine. 2010 ; Vol. 16, No. 10. pp. 1128-1133.
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