Abstract
Giant cell arteritis (GCA) is a systemic granulomatous vasculitis clinically characterized by a prompt response to glucocorticoid therapy. Dendritic cells (DCs) play a central role in the pathogenesis of the disease and are increased in temporal arteries from GCA patients. The aim of this study was to determine the effects of glucocorticoid therapy on granulomatous infiltrates and on peripheral DCs of GCA patients. Immunohistochemical staining of temporal artery specimens from 41 GCA patients revealed a rapid reduction of the number of DCs after initiation of glucocorticoid treatment. TUNEL staining was performed to quantify apoptotic S100+ DC, CD3+ T cells, and CD68+ macrophages in the granulomatous infiltrates. An increase of apoptotic cells up to 9 ± 2% after 4–5 days of glucocorticoid therapy and up to 27 ± 5% (p < 0.001, compared to earlier timepoints) after 6–10 days was detected. A decrease of CCL19 and CCL21 expression was observed after starting glucocorticoid therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also significantly decreased under glucocorticoid therapy. No GM-CSF expression was detected in the control specimens. Glucocorticoid therapy leads to a rapid, time-dependent reduction of DCs in temporal arteries from GCA patients and reduction of mediators for cell migration. Our data suggest GM-CSF as a novel therapeutic target of GCA.
Highlights
Giant cell arteritis (GCA) is a vasculitis predominantly affecting medium- and large-sized arteries
An increase of monocyte-macrophage scavenger receptor CD163 was observed under glucocorticoid therapy that inversely correlates with the number of S100+ cells and the duration of glucocorticoid exposure (Figure 1A)
Administration of glucocorticoids suppresses the accumulation of Dendritic cells (DCs) and leads to a rapid, time-dependent normalization of DCs in temporal arteries from GCA patients
Summary
GCA is a vasculitis predominantly affecting medium- and large-sized arteries. DCs play a significant role in the pathogenesis of large vessel vasculitides. Studies of large-vessel vasculitis have shown that activation of tissue residing DCs causes T cell and macrophage activation that subsequently leads to granuloma formation in the vessel wall [1]. Previous data showed the immediate neighborhood of DCs and activated CD4+ T cells in inflammatory lesions of temporal artery specimens from GCA patients indicating that there was a high probability of DCs being the key antigen presenting cells in GCA [3]. It was shown that activated DCs stimulate autologous CD4 T cells, which produce the proinflammatory cytokine interferon-gamma (IFN-γ) and infiltrate deeply into the vascular smooth muscle cell layer, causing matrix damage [4].
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