Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid.

Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid.
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DOI:
10.4049/jimmunol.1001233
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发表时间:
2010-11-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Elson CO
Elson CO
中科院分区:
其他
文献类型:
--
作者:
Feng T;Cong Y;Qin H;Benveniste EN;Elson CO

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目前尚不清楚树突状细胞 (DC) 如何专门化为粘膜 DC 并维持肠道稳态。我们报道骨髓细胞表达视黄酸(RA)合成酶 ALDH1a2,并为骨髓微环境中的 DC 前体提供 RA。 RA 诱导骨髓源性 DC (BMDC) 表达 CCR9 和 ALDH1a2,并赋予它们粘膜 DC 功能。这取决于狭窄的时间窗和严格的剂量效应。 RA 通过抑制 SOCS3 表达,从而增强 STAT3 激活,促进 BMDC 产生生物活性 TGF-β。这些 RA 效应在体内很明显,因为缺乏维生素 A 的粘膜 DC 会降低粘膜功能,即无法诱导 Foxp3+ 调节性 T 细胞。最后,MyD88 信号传导增强了 RA 诱导的 DC ALDH1a2 表达,并且是 TGF-β 产生所必需的。这些数据表明 RA 在骨髓粘膜 DC 的生成及其功能活性中发挥着关键作用。
It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that bone marrow cells express the retinoic acid (RA)-synthesizing enzyme ALDH1a2, and provide RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs (BMDCs) to express CCR9 and ALDH1a2, and conferred upon them mucosal DC functions. This was dependent on a narrow time window and stringent dose effect. RA promoted BMDC production of bioactive TGF-β by inhibiting SOCS3 expression and hence enhancing STAT3 activation. These RA effects were evident in vivo, in that vitamin A-deficient mucosal DCs had reduced mucosal function, namely failure to induce Foxp3+ regulatory T cells. Lastly, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression, and was required for TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow as well as in their functional activity.
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