Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells.

Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells.
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DOI:
10.1038/mi.2014.51
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发表时间:
2015-01
期刊:
影响因子:
8
通讯作者:
--
中科院分区:
医学1区
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肠道中的粘膜树突状细胞(DC)具有产生维甲酸(RA)的独特能力,维甲酸是一种维生素A代谢物,可诱导肠道趋向性并调节其启动的T细胞的功能分化。在此,我们在肠道固有层(LP)中发现了一个基质细胞(SC)群,它能够以依赖RA和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的方式诱导DC产生RA。与DC不同,LP SCs即使在缺乏膳食维生素A的情况下也能结构性地表达产生RA的酶机制,但在无菌小鼠中无法表达,这意味着受到微生物区系的调控。有趣的是,DC通过干细胞促进GM-CSF的产生,表明两种细胞类型之间存在双向串扰。此外,产生RA的LP SC和肠道DC在体内的分布非常密切,提示这两种细胞之间的相互作用可能在移行DC的功能教育中发挥重要作用,从而在调节对口腔和共生抗原的免疫反应中发挥重要作用。
Mucosal dendritic cells (DCs) in the intestine acquire the unique capacity to produce retinoic acid (RA), a vitamin A metabolite that induces gut tropism and regulates the functional differentiation of the T cells they prime. Here we identified a stromal cell (SC) population in the intestinal lamina propria (LP), which is capable of inducing RA production in DCs in a RA- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent fashion. Unlike DCs, LP SCs constitutively expressed the enzymatic machinery to produce RA even in the absence of dietary vitamin A but were not able to do so in germ-free mice implying regulation by microbiota. Interestingly, DCs promoted GM-CSF production by the SCs indicating a two-way crosstalk between both cell types. Furthermore, RA-producing LP SCs and intestinal DCs localized closely in vivo suggesting that the interactions between both cell types might play an important role on the functional education of migratory DCs and therefore in the regulation of immune responses towards oral and commensal antigens.
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