首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro
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Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro

机译:炎症条件明显改变了朗格汉斯样细胞和树突状细胞的免疫功能

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The specific function of human skin-resident dendritic cell (DC) subsets in the regulation of immunity or tolerance is still a matter of debate. Langerhans cells (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain tolerance to bacteria. However, the definite function of epidermal LC and cutaneous DC appears even more complex under inflammatory conditions. Here we investigated the immune responses of human immature monocyte-derived DC (MoDC) and LC-like cells (MoLC) upon stimulation with different Toll-like receptor ligands in the presence or absence of pro-inflammatory cytokines tumour necrosis factor- (TNF-) and interleukin-1 (IL-1). In MoDC, bacterial antigens selectively up-regulated CD83 and CD86 expression and induced the release of T helper type 1 (Th1) and Th17 cytokines and led to a higher CCR7-dependent migratory capacity compared with a low responsiveness of MoLC. Importantly, MoLC activation with lipopolysaccharide under inflammatory conditions strongly enhanced a phenotypically mature state, increased IL-12p70, IL-23 and IL-6 production and Th1 cytokine secretion by CD4(+) T cells. Treatment with poly(I:C) specifically up-regulated surface expression of co-stimulatory molecules and increased release of IL-12p70 in MoLC and co-stimulation with TNF- and IL-1 further elevated Th1 and Th17 cytokine production. Poly(I:C)-induced up-regulation of type I interferon mRNA levels in MoLC and MoDC was Toll-like receptor 3-dependent but not, or only weakly, modulated by pro-inflammatory cytokines. Our results indicate that inflammatory conditions greatly facilitate recognition of bacteria by MoLC. Furthermore, we suggest a critical involvement of both subsets in innate defence against viruses, whereas inflammatory skin environments additionally favour MoLC as potent inducers of Th1 and Th17 cytokines.
机译:人类皮肤驻留树突状细胞(DC)亚群在调节免疫或耐受性方面的具体功能仍是一个争论的问题。朗格汉斯细胞(LC)诱导抗病毒免疫反应,但与真皮DC相反,保持对细菌的耐受性。然而,在炎症条件下,表皮LC和皮肤DC的确定功能显得更为复杂。在这里,我们研究了在存在或不存在促炎性细胞因子肿瘤坏死因子-(TNF-)的情况下,用不同的Toll-like受体配体刺激后,人类未成熟单核细胞衍生DC(MoDC)和LC-like细胞(MoLC)的免疫反应。 )和白介素1(IL-1)。在MoDC中,细菌抗原选择性地上调CD83和CD86的表达并诱导1型T辅助细胞(Th1)和Th17细胞因子的释放,并导致与CLC7依赖的迁移能力更高,而MoLC的响应性却较低。重要的是,在炎症条件下用脂多糖进行的MoLC活化可强烈增强表型成熟状态,增加IL-12p70,IL-23和IL-6的产生以及CD4(+)T细胞分泌Th1细胞因子。用聚(I:C)处理可特异性上调共刺激分子的表面表达,并增加MoLC中IL-12p70的释放以及与TNF-和IL-1的共刺激,进一步提高了Th1和Th17细胞因子的产生。聚(I:C)诱导的MoLC和MoDC中I型干扰素mRNA水平的上调是Toll样受体3依赖性的,但不受促炎细胞因子的调节,或仅受促炎性细胞因子调节的程度很弱。我们的结果表明,炎症条件极大地促进了MoLC对细菌的识别。此外,我们建议这两个子集都在与病毒的先天防御中起关键作用,而炎症性皮肤环境还支持MoLC作为Th1和Th17细胞因子的有效诱导剂。

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