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Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment

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Published:25th Mar 2020
Background: Plasmacytoid dendritic cells (pDCs) infiltrate sites of acute Th2-dominant inflammation but their role in allergic asthma remains unclear. Objective: To characterise circulating pDCs from patients with allergic asthma outside their respective allergen season. Methods: Adhesion molecules, co-stimulatory molecules, immunoglobulin receptors, and chemokine receptors were quantified on blood pDCs from 20 patients with allergic asthma and 18 healthy controls by flow cytometry. In addition, IL-6-, TNF-?-, and IFN-?-secretion was analysed after stimulating isolated pDCs with TLR7- and TLR9-ligands. Results: PDCs from patients with allergic asthma showed an increased expression of chemokine receptors involved in inflamed tissue homing such as CCR2, CCR4, CCR9, CCR10, CXCR2, CXCR5, and CXCR6, while the expression of the lymph node homing receptor CXCR3 was downregulated. In addition, these pDCs exhibited a higher expression of activation markers and Th2-associated molecules such as CD40, CD62L, CD64, and Fc?RI?. In contrast, TLR7-mediated IL-6-, TNF-?-, and IFN-?-secretion was significantly reduced in pDCs from patients with asthma. The TLR9-mediated cytokine response was only suppressed in those patients who were treated with inhaled corticosteroids (ICS) during previous allergen seasons. The same effect was observed for CD54 and OX40L expression. Conclusions: We report an increased expression of activation markers, and Th2-associated molecules, and an increased migratory potential of circulating pDCs in allergic asthma. These changes are accompanied by a reduced TLR7-mediated cytokine response. In addition, our results suggest a longterm impact of ICS treatment on the characteristics of circulating pDCs.

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