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

98 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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1'. Together they form a unique fingerprint.

  • Cite this

    Zhou, Y., Kawasaki, H., Hsu, S. C., Lee, R. T., Yao, X., Plunkett, B., Fu, J., Yang, K., Lee, Y. C., & Huang, S. K. (2010). Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. Nature Medicine, 16(10), 1128-1133. https://doi.org/10.1038/nm.2201