Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigen-specific Th2 response
Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigen-specific Th2 response
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DOI：
10.1189/jlb.1210696
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发表时间：
2011-10-01
影响因子：
5.5
通讯作者：
Yang, Ping-Chang
中科院分区：
文献类型：
--
作者：
Chen, Xiao;Song, Chun-Hua;Yang, Ping-Chang
耐药树突状细胞和树突状细胞被认为在口腔耐受中起关键作用。然而，肠道中产生耐受树突状细胞和激活Tregs的机制仍然知之甚少。本研究旨在探讨IECS和蛋白质抗原诱导功能性耐受树突状细胞和树突状细胞的分子机制。用体外和体内方法研究了肠上皮细胞来源的外切体αvβ6的表达及其与食物抗原的偶联，以及它们与功能性耐受树突状细胞和树突状细胞发育的关系。结果表明，IECS在摄取抗原时上调了整合素αvβ6的表达。上皮细胞来源的外切体将αvβ6和抗原包裹并运输到细胞外环境中。抗原的单独摄取诱导DC产生LTGF-β，而携带αv-β6/抗原的外体则导致DC产生丰富的、活性的转化生长因子-β，从而赋予DC耐受特性。此外，研究还发现，携带αvβ6/OVA、外切体诱导的DC可促进树突状细胞产生活性的转化生长因子-β。因此，体内注射携带αvβ6/OVA的外切体可诱导肠道中Tregs的产生，并抑制对食物抗原的偏斜Th2反应。我们的研究展示了携带αvβ6和食物抗原的IEC来源的外切体在诱导耐受树突状细胞和抗原特异性树突状细胞中的重要作用，从而为Treg的分子机制提供了重要的分子见解。J.Leukoc。比奥尔。90：751-759；2011。
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 alpha v beta 6 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 alpha v beta 6 upon uptake of antigens. The epithelial cell-derived exosomes entrapped and transported alpha v beta 6 and antigens to the extracellular environment. The uptake of antigens alone induced DCs to produce LTGF beta, whereas exosomes carrying alpha v beta 6/antigen resulted in the production of abundant, active TGF-beta in DCs that conferred to DCs the tolerogenic properties. Furthermore, alpha v beta 6/OVA-carrying, exosome-primed DCs were found to promote the production of active TGF-beta in Tregs. Thus, in vivo administration of alpha v beta 6/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 alpha v beta 6 and food antigen in the induction of tolerogenic DCs and antigen-specific Tregs. J. Leukoc. Biol. 90: 751-759; 2011.