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

类风湿性关节炎与其他慢性炎症性疾病相似，可检测到下丘脑-垂体-肾上腺(HPA)轴功能恶化，表现为糖皮质激素分泌不足，与炎症严重程度有关。下丘脑、脑下垂体和肾上腺水平的变化导致肾上腺功能障碍。到目前为止，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负责因素。然而，我们的初步结果表明，免疫细胞渗入肾上腺，从而直接免疫-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因素，这可能对关节炎时糖皮质激素的产生产生不利影响。在本项目中，我们将在体外详细研究在健康和关节炎DA大鼠肾上腺中发现的表达II类MHC的树突状细胞与肾上腺皮质细胞之间的相互作用。此外，我们还将在体内鉴定这些肾上腺树突状细胞的来源和迁移模式。最后，我们将检查，肾上腺内树突状细胞的枯竭是否导致II型胶原诱导的关节炎的改善。这些实验旨在阐明关节炎期间肾上腺无法产生糖皮质激素的机制。

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.