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

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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.