Cutting edge: inhaled antigen upregulates retinaldehyde dehydrogenase in lung CD103+ but not plasmacytoid dendritic cells to induce Foxp3 de novo in CD4+ T cells and promote airway tolerance.

Cutting edge: inhaled antigen upregulates retinaldehyde dehydrogenase in lung CD103+ but not plasmacytoid dendritic cells to induce Foxp3 de novo in CD4+ T cells and promote airway tolerance.
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DOI:
10.4049/jimmunol.1300193
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发表时间:
2013-07-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Ray A
Ray A
中科院分区:
其他
文献类型:
--
作者:
Khare A;Krishnamoorthy N;Oriss TB;Fei M;Ray P;Ray A

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树突状细胞(DC)-T细胞相互作用是iTreg产生和气道耐受性的基础,但尚未得到很好的理解。在这里,我们表明,缺乏CD 11集落肺DCs,但含有pDCs的小鼠不能耐受吸入抗原,不能支持Foxp 3诱导体内幼稚的CD 4 + T细胞。来自耐受小鼠的CD 103 + DC在共培养的幼稚CD 4 + T细胞中有效地诱导Foxp 3,但pDC和肺巨噬细胞不能这样做。CD 103 + DC,而不是pDC或肺巨噬细胞,上调了视黄醛脱氢酶2(aldh 1a 2)的表达,这是产生视黄酸的关键,视黄酸是Foxp 3诱导的TGF-β的辅因子。选择性缺乏CD 103 + DCs的Batf 3 −/−小鼠未能通过吸入抗原耐受。总的来说,我们的数据显示肺耐受依赖于CD 103 + DC,与它们上调aldh 1a 2的能力相关,这可以促进T细胞中FoxP 3的表达。
Dendritic cell (DC)-T cell interactions that underlie iTreg generation and airway tolerance are not well understood. Here we show that mice lacking CD11chi lung DCs but containing pDCs fail tolerization with inhaled antigen and cannot support Foxp3 induction in vivo in naïve CD4+ T cells. CD103+ DCs from tolerized mice efficiently induced Foxp3 in co-cultured naïve CD4+ T cells but pDCs and lung macrophages failed to do so. CD103+ DCs, but not pDCs or lung macrophages, upregulated expression of retinaldehyde dehydrogenase 2 (aldh1a2) that is key for production of retinoic acid, a co-factor for TGF-β for Foxp3 induction. Batf3−/− mice, selectively lacking CD103+ DCs, failed tolerization by inhaled antigen. Collectively, our data show that pulmonary tolerance is dependent on CD103+DCs, correlating with their ability to upregulate aldh1a2, which can promote FoxP3 expression in T cells.
过敏原激发期间肺 CD11c+ 树突状细胞的体内耗竭消除了哮喘的特征。
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