β8 Integrin Expression and Activation of TGF-β by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage.
β8 Integrin Expression and Activation of TGF-β by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage.
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DOI：
10.4049/jimmunol.1600244
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发表时间：
2016-09-01
期刊：
影响因子：
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通讯作者：
Paidassi H
中科院分区：
文献类型：
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作者：
Boucard-Jourdin M;Kugler D;Endale Ahanda ML;This S;De Calisto J;Zhang A;Mora JR;Stuart LM;Savill J;Lacy-Hulbert A;Paidassi H
表达αvβ8整联蛋白的树突状细胞（DC）激活TGF-β对于产生肠道调节性T细胞（TCRs）是必不可少的，而TCRs又促进对肠道抗原的耐受。我们最近发现αvβ8整合素优先由CD 103 + DC表达，并赋予其激活TGF-β和产生TGF 3的能力。然而，这些树突状细胞如何成为专门的这一重要功能是未知的。在这里，我们表明β8表达受多种因素的组合控制，包括DC谱系，以及来自组织微环境和微生物群的信号。具体而言，我们的数据表明，TGF-β本身，沿着与视黄酸（RA）和Toll样受体（TLR）信号传导，驱动αvβ8在DC中的表达。然而，这些信号仅导致CD 8 α+或CD 103 + CD 11b − DC细胞中β8的高水平表达，这与Itgb 8基因座的表观遗传变化有关。总之，这些数据提供了一个关键的说明性实例，说明微环境因素和细胞谱系如何驱动表达调节性αvβ8的DC的生成，这些DC专门用于活化TGF-β以促进Treg生成。
Activation of TGF-β by dendritic cells (DCs) expressing αvβ8 integrin is essential for the generation of intestinal regulatory T cells (Tregs) that in turn promote tolerance to intestinal antigens. We have recently shown that αvβ8 integrin is preferentially expressed by CD103+ DCs, and confers their ability to activate TGF-β and generate Tregs. However, how these DCs become specialized for this vital function is unknown. Here we show that β8 expression is controlled by a combination of factors that include DC lineage, and signals derived from the tissue microenvironment and microbiota. Specifically, our data demonstrate that TGF-β itself, along with retinoic acid (RA) and Toll-like receptor (TLR) signaling, drive expression of αvβ8 in DCs. However, these signals only result in high levels of β8 expression in cells of the cDC1 lineage, CD8α+ or CD103+CD11b− DCs, and this is associated with epigenetic changes in the Itgb8 locus. Together, these data provide a key illustrative example of how microenvironmental factors and cell lineage drive the generation of regulatory αvβ8-expressing DCs specialized for activation of TGF-β to facilitate Treg generation.