Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment
Article first published online: 17 FEB 2013
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 43, Issue 3, pages 312–321, March 2013
How to Cite
Clinical & Experimental Allergy, 2013 (43) 312–321., , , , , ,
- Issue published online: 17 FEB 2013
- Article first published online: 17 FEB 2013
- Accepted manuscript online: 22 NOV 2012 07:11PM EST
- Manuscript Accepted: 2 NOV 2012
- Manuscript Revised: 19 OCT 2012
- Manuscript Received: 9 MAY 2012
- Deutsche Forschungsgemeinschaft . Grant Number: 3649/1-1
- asthma, chemokine receptor, inhaled corticosteroids;
- plasmacytoid dendritic cells, toll-like receptor
Plasmacytoid dendritic cells (pDCs) infiltrate sites of acute Th2-dominant inflammation, but their role in allergic asthma remains unclear.
To characterize circulating pDCs from patients with allergic asthma outside their respective allergen season.
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 using flow cytometry. In addition, IL-6-, TNF-α- and IFN-α-secretion were analysed after stimulating isolated pDCs with TLR7- and TLR9-ligands.
Plasmacytoid dendritic cells 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 down-regulated. In addition, these pDCs exhibited a higher expression of activation markers and Th2-associated molecules such as CD40, CD62L, CD64 and FcεRIα. In contrast, TLR7-mediated IL-6-, TNF-α- and IFN-α-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.
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.