Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigenspecific TH2 response

Xiao Chen, Chun Hua Song, Bai Sui Feng, Tong Li Li, Ping Li, Peng Yuan Zheng, Xian-Ming Chen, Zhou Xing, Ping Chang Yang

Research output: Contribution to journalArticle

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Abstract

Toleroge nic DCs and Tregs are believed to play a critical role in oral tolerance. However, the mechanisms of the generation of tolerogenic DCs and activation of Tregs in the gut remain poorly understood. This study aims to dissect the molecular mechanisms by which IECs and protein antigen induce functional tolerogenic DCs and Tregs. Expression of αvβ6 by gut epithelial cell-derived exosomes, its coupling with food antigen, and their relationship with the development of functional tolerogenic DCs and Tregs were examined by using in vitro and in vivo approaches. The results show that IECs up-regulated the integrin αvβ6 upon uptake of antigens. The epithelial cell-derived exosomes entrapped and transported αvβ6 and antigens to the extracellular environment. The uptake of antigens alone induced DCs to produce LTGFβ, whereas exosomes carrying αvβ6/antigen resulted in the production of abundant, active TGF-β in DCs that conferred to DCs the tolerogenic properties. Furthermore, αvβ6/OVA-carrying, exosome-primed DCs were found to promote the production of active TGF-β in Tregs. Thus, in vivo administration of αvβ6/OVA-laden exosomes induced the generation of Tregs and suppressed skewed Th2 responses toward food antigen in the intestine. Our study provides important molecular insights into the molecular mechanisms of Treg development by demonstrating an important role of IEC-derived exosomes carrying αvβ6 and food antigen in the induction of tolerogenic DCs and antigen-specific Tregs.

Original languageEnglish
Pages (from-to)751-759
Number of pages9
JournalJournal of Leukocyte Biology
Volume90
Issue number4
DOIs
StatePublished - Oct 2011

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Regulatory T-Lymphocytes
Integrins
Exosomes
Epithelial Cells
Antigens
Food
Intestines

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Immunology

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Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigenspecific TH2 response. / Chen, Xiao; Song, Chun Hua; Feng, Bai Sui; Li, Tong Li; Li, Ping; Zheng, Peng Yuan; Chen, Xian-Ming; Xing, Zhou; Yang, Ping Chang.

In: Journal of Leukocyte Biology, Vol. 90, No. 4, 10.2011, p. 751-759.

Research output: Contribution to journalArticle

Chen, Xiao ; Song, Chun Hua ; Feng, Bai Sui ; Li, Tong Li ; Li, Ping ; Zheng, Peng Yuan ; Chen, Xian-Ming ; Xing, Zhou ; Yang, Ping Chang. / Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigenspecific TH2 response. In: Journal of Leukocyte Biology. 2011 ; Vol. 90, No. 4. pp. 751-759.
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abstract = "Toleroge nic DCs and Tregs are believed to play a critical role in oral tolerance. However, the mechanisms of the generation of tolerogenic DCs and activation of Tregs in the gut remain poorly understood. This study aims to dissect the molecular mechanisms by which IECs and protein antigen induce functional tolerogenic DCs and Tregs. Expression of αvβ6 by gut epithelial cell-derived exosomes, its coupling with food antigen, and their relationship with the development of functional tolerogenic DCs and Tregs were examined by using in vitro and in vivo approaches. The results show that IECs up-regulated the integrin αvβ6 upon uptake of antigens. The epithelial cell-derived exosomes entrapped and transported αvβ6 and antigens to the extracellular environment. The uptake of antigens alone induced DCs to produce LTGFβ, whereas exosomes carrying αvβ6/antigen resulted in the production of abundant, active TGF-β in DCs that conferred to DCs the tolerogenic properties. Furthermore, αvβ6/OVA-carrying, exosome-primed DCs were found to promote the production of active TGF-β in Tregs. Thus, in vivo administration of αvβ6/OVA-laden exosomes induced the generation of Tregs and suppressed skewed Th2 responses toward food antigen in the intestine. Our study provides important molecular insights into the molecular mechanisms of Treg development by demonstrating an important role of IEC-derived exosomes carrying αvβ6 and food antigen in the induction of tolerogenic DCs and antigen-specific Tregs.",
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