Role of dendritic cells in adrenal glands of healthy and arthritic rats

树突状细胞在健康和关节炎大鼠肾上腺中的作用

• 批准号: 235438724
• 负责人: Professor Dr. Rainer H. Straub
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/235438724?language=en
• 关键词: Role; dendritic; cells; adrenal; glands

In rheumatoid arthritis, similar as in other chronic inflammatory diseases, a functional deterioration of the hypothalamic-pituitary-adrenal (HPA) axis in form of inadequately low secretion of glucocorticoids in relation to severity of inflammation can be detected. Changes on the level of the hypothalamus, pituitary gland and adrenal gland contribute to adrenal dysfunction. To date, proinflammatory cytokines seem to be the main responsible factors for inability of adrenal glands to produce adequate amounts of steroid hormones during arthritis. Our preliminary results, however, suggest that immune cell infiltration into the adrenal gland and hence direct immune-adrenal crosstalk as well as adrenocortical mitochondrial dysfunction can be important stimuli to disrupt the normal function of the adrenal glands, which can influence glucocorticoid production during arthritis in a negative unfavourable way.In this project, we will investigate in detail the interactions between class II MHC-expressing dendritic cells found in the adrenal glands and adrenocortical cells from healthy and arthritic DA rats in vitro. Moreover, we will characterize the origin and the migration patterns of those adrenal dendritic cells in vivo. Finally, we will examine, if intra-adrenal depletion of dendritic cells results in an improvement of collagen type II induced arthritis. These experiments aim to elucidate mechanisms underlying the inability of adrenal glands to produce glucocorticoids during arthritis.

在类风湿性关节炎中，与其他慢性炎性疾病相似，可以检测到下丘脑-垂体-肾上腺（HPA）轴的功能恶化，其形式为与炎症严重程度相关的糖皮质激素分泌不足。下丘脑、垂体和肾上腺水平的变化有助于肾上腺功能障碍。迄今为止，促炎细胞因子似乎是关节炎期间肾上腺无法产生足够量的类固醇激素的主要原因。然而，我们的初步结果表明，免疫细胞浸润到肾上腺中，因此直接免疫肾上腺串扰以及肾上腺皮质线粒体功能障碍可能是破坏肾上腺正常功能的重要刺激，这可能以负面不利的方式影响关节炎期间糖皮质激素的产生。我们将在体外详细研究在健康和关节炎DA大鼠的肾上腺和肾上腺皮质细胞中发现的表达II类MHC的树突状细胞之间的相互作用。此外，我们将描述这些肾上腺树突状细胞在体内的起源和迁移模式。最后，我们将检查，如果肾上腺内耗尽树突状细胞的结果在改善胶原蛋白II型诱导的关节炎。这些实验旨在阐明关节炎时肾上腺不能产生糖皮质激素的机制。