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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice
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Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice

机译：从紫外线照射小鼠的骨髓中分化出来的调节性树突状细胞的表征

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When antigen-loaded dendritic cells (DCs) differentiated from the bone marrow (BM) of UV-irradiated mice (UV-BMDCs) were adoptively transferred into naive mice or mice pre-sensitized with that antigen, the recipients exhibited a reduced immune response following antigen challenge. Hence, UV-BMDCs are poorly immunogenic and can suppress pre-existing immunity. The UV-induced effect on BM-derived DCs was rapid (observed 1 day after UV radiation), long-lasting (observed 10 days after UV radiation) and UV dose-dependent. The mechanism by which UV-BMDCs could regulate immunity was investigated. The CD11c+ cells, differentiated using granulocyte-macrophage colony-stimulating factor + interleukin-4, were confirmed to be DCs because they did not express the myeloid-derived suppressor cell marker, Gr1. UV-BMDCs did not display altered antigen uptake, processing or ability to activate T cells in vitro. When gene expression in UV-BMDCs and DCs differentiated from the BM of non-irradiated mice (control-BMDCs) was examined, Ccl7, Ccl8 and CSF1R (CD115) mRNA transcripts were up-regulated in UV-BMDCs compared with control-BMDCs. However, neutralizing antibodies for Ccl7 and Ccl8 did not abrogate the reduced immunogenicity of UV-BMDCs in vivo. Moreover, the up-regulation of CSF1R transcript did not correspond with increased receptor expression on UV-BMDCs. The phenotypes of UV-BMDCs and control-BMDCs were similar, with no difference in the expression of CD4, CD8α, CD103, B220 or F4/80, or the regulatory molecules CCR7 (CD197), FasL (CD95L), B7H3 (CD276) and B7H4. However, PDL1 (CD274) expression was reduced in UV-BMDCs compared with control-BMDCs following lipopolysaccharide stimulation. In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'.
机译：当从紫外线照射的小鼠的骨髓（BM）分化而来的抗原加载的树突状细胞（DC）被过继转移到幼稚小鼠或被该抗原预敏的小鼠中时，接受者在随后的免疫反应降低抗原攻击。因此，UV-BMDCs的免疫原性很差，可以抑制现有的免疫力。紫外线对BM衍生DC的诱导作用迅速（在紫外线辐射后1天观察到），持续时间长（在紫外线辐射后10天观察到）且与紫外线剂量有关。研究了UV-BMDC调节免疫力的机制。使用粒细胞-巨噬细胞集落刺激因子+白细胞介素4分化的CD11c +细胞被确认为DC，因为它们不表达源自髓样的抑制细胞标记物Gr1。 UV-BMDC在体外没有显示出改变的抗原吸收，加工或激活T细胞的能力。当检查了UV-BMDC和DC的基因表达与未辐照小鼠的BM区别时（对照BMDC），与对照BMDC相比，UV-BMDC中的Ccl7，Ccl8和CSF1R（CD115）mRNA转录上调了。但是，Ccl7和Ccl8的中和抗体不能消除体内UV-BMDCs降低的免疫原性。此外，CSF1R转录本的上调并不与UV-BMDCs上受体表达的增加相对应。 UV-BMDC和对照BMDC的表型相似，CD4，CD8α，CD103，B220或F4 / 80或调节分子CCR7（CD197），FasL（CD95L），B7H3（CD276）的表达无差异和B7H4。但是，与脂多糖刺激后的对照组相比，UV-BMDC中的PDL1（CD274）表达降低。总之，UV-BMDC不表达DC的经典表型或基因表达特性，而其他人将其报告为“调节性”或“致耐受性”。

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