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Reduced airway inflammation in CD26/DPP4-deficient F344 rats is associated with altered recruitment patterns of regulatory T cells and expression of pulmonary surfactant proteins.

机译:CD26 / DPP4缺陷型F344大鼠气道炎症的减少与调节性T细胞募集模式的改变和肺表面活性物质蛋白的表达有关。

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INTRODUCTION: CD26 is highly expressed on lung epithelial cells as well as on immune cells. Ovalbumin (OVA)-induced airway inflammation induces a further increase of CD26 expression. CD26-deficient rat strains exhibit blunted clinical courses in models of experimental asthma. OBJECTIVE: (1) To investigate the involvement of regulatory T cells (Tregs) and the surfactant system in a rat model of genetic CD26 deficiency. (2) To investigate regulatory mechanisms dependent on the endogenous CD26 expression. (3) To investigate the impact of CD26 on surfactant protein (SP)-levels under inflammatory conditions. METHODS: Wild-type and CD26-deficient F344 rats were sensitized to and challenged with OVA. Subsequently, airway inflammation, SP levels as well as surface tension of the bronchoalveolar lavage (BAL) fluid were evaluated. RESULTS: CD26 deficiency led to decreased airway inflammation, e.g. reduced numbers of eosinophils and activated T cells in the BAL. Remarkably, the CD26-deficient rats exhibited a significantly increased influx of FoxP3(+) Tregs into the lungs and increased IL-10-secretion/production by draining lymph node cells in culture experiments. Furthermore, in OVA-challenged CD26-deficient rats, the increase of the expression of the collectins SP-A and SP-D as well as of the surface tension-active SP-B was significantly less pronounced than in the CD26-positive strain. Only in the wild-type rats, functional alterations of the surfactant system, e.g. the increased surface tension were obvious after OVA challenge. CONCLUSION: Reduced airway inflammation in CD26-deficient F344 rats appear to be mediated by differences in the recruitment and activity of Tregs. This altered inflammation is associated with differences in the SP expression as well as function.
机译:简介:CD26在肺上皮细胞和免疫细胞上高表达。卵清蛋白(OVA)诱导的气道炎症诱导CD26表达的进一步增加。缺乏CD26的大鼠品系在实验性哮喘模型中表现出钝化的临床过程。目的:(1)研究调节性T细胞(Tregs)和表面活性剂系统在遗传性CD26缺乏症大鼠模型中的作用。 (2)研究依赖于内源性CD26表达的调控机制。 (3)研究在炎症条件下CD26对表面活性蛋白(SP)水平的影响。方法:野生型和CD26缺陷型F344大鼠对OVA敏感并攻击。随后,评估气道炎症,SP水平以及支气管肺泡灌洗液(BAL)的表面张力。结果:CD26缺乏症导致气道炎症减少,例如减少了BAL中嗜酸性粒细胞和活化T细胞的数量。值得注意的是,在培养实验中,CD26缺陷型大鼠表现出明显增加的FoxP3(+)Treg流入肺部,并通过排空淋巴结细胞而增加了IL-10分泌/产生。此外,在OVA攻击的CD26缺陷型大鼠中,collectins SP-A和SP-D以及表面张力活性SP-B的表达增加明显不如CD26阳性菌株。仅在野生型大鼠中,表面活性剂系统的功能发生改变,例如在OVA攻击后表面张力增加明显。结论:缺乏CD26的F344大鼠气道炎症的减轻似乎是由Treg募集和活性的差异所介导的。这种改变的炎症与SP表达以及功能的差异有关。

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