Epithelia Use Butyrophilin-like Molecules to Shape Organ-Specific γδ T Cell Compartments.
Epithelia Use Butyrophilin-like Molecules to Shape Organ-Specific γδ T Cell Compartments.
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DOI：
10.1016/j.cell.2016.08.030
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发表时间：
2016-09-22
期刊：
影响因子：
64.5
通讯作者：
Hayday, Adrian
中科院分区：
文献类型：
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作者：
Barros, Rafael Di Marco;Roberts, Natalie A.;Dart, Robin J.;Vantourout, Pierre;Jandke, Anett;Nussbaumer, Oliver;Deban, Livija;Cipolat, Sara;Hart, Rosie;Iannitto, Maria Luisa;Laing, Adam;Spencer-Dene, Bradley;East, Philip;Gibbons, Deena;Irving, Peter M.;Pereira, Pablo;Steinhoff, Ulrich;Hayday, Adrian
许多身体表面都有器官特异性的γδT细胞隔间，有助于组织的完整性。因此，唯一表达T细胞受体(TcR)-Vγ5链的小鼠树突状表皮T细胞(DETCs)可以保护皮肤免受致癌物的伤害。DETC谱系由Skint1形成，Skint1是一种由胸腺上皮细胞和超基底角质形成细胞特异性表达的类丁咯菲林(Btnl)基因。然而，这种机制的普遍性仍然不透明，因为无论是Skint1还是DETCs在进化上都不是保守的。在这里，由小鼠肠细胞表达的Btnl1被证明形成了局部的TcR-Vγ7+γδ隔室。这种活性不受微生物或食物抗原的影响，引起TCRαβ+谱系的发育选择。事实上，Btnl1和Btnl6共同在肠道Vγ7+细胞中特异性地诱导TcR依赖的反应。同样，人肠上皮细胞表达BTnL3和BTnL8，共同诱导人结肠Vγ4+细胞的选择性TcR依赖反应。因此，出现了一种保守的机制，即上皮细胞使用器官特异性的BTnL/Btnl基因来塑造局部T细胞隔间。肠上皮类酪氨酸样蛋白1(Btnl1)塑造局部γδT细胞亚室，其他器官特异性上皮性BTn1基因选择其他部位的同源γδ细胞，Btn1异构体可以特异地激活具有同源T细胞受体的γδT细胞。人BTn1基因揭示了上皮T细胞调节的保守生物学，上皮细胞提供信号，指导其局部γδT细胞亚室的发育和功能，使这些免疫细胞能够支持不同屏障组织的非免疫功能。
Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved. Here, Btnl1 expressed by murine enterocytes is shown to shape the local TCR-Vγ7+ γδ compartment. Uninfluenced by microbial or food antigens, this activity evokes the developmental selection of TCRαβ+ repertoires. Indeed, Btnl1 and Btnl6 jointly induce TCR-dependent responses specifically in intestinal Vγ7+ cells. Likewise, human gut epithelial cells express BTNL3 and BTNL8 that jointly induce selective TCR-dependent responses of human colonic Vγ4+ cells. Hence, a conserved mechanism emerges whereby epithelia use organ-specific BTNL/Btnl genes to shape local T cell compartments. Gut epithelial butyrophilin-like 1 (Btnl1) shapes the local γδ T cell compartment Other organ-specific epithelial Btnl genes select cognate γδ cells in other sites Btnl heteromers can specifically activate γδ T cells with cognate T cell receptors Human BTNL genes reveal a conserved biology of epithelial T cell regulation Epithelial cells provide signals that instruct the development and function of their local γδ T cell compartments so that these immune cells can support the non-immune functions of the different barrier tissues.
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影响因子：
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作者：
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发表时间：
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