| Autor: |
K, Bratke, J, Nielsen, F, Manig, C, Klein, M, Kuepper, S, Geyer, P, Julius, M, Lommatzsch, J C, Virchow |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 40(7) |
| ISSN: |
1365-2222 |
| Popis: |
Plasmacytoid dendritic cells (pDCs) are involved in a variety of immune functions. However, the expression of cytotoxic granule proteins like granzymes and perforin in human pDCs is still poorly understood.The aim of this study was to systematically analyse the expression and regulation of cytotoxic granule proteins in human pDCs.The expression of cytotoxic proteins was analysed by RT-PCR, flow cytometry, and fluorescence microscopy. The functional expression of these proteins was confirmed in a flow-cytometry-based cytotoxicity assay using K562 cells as targets. In order to analyse the regulation of pDC-derived cytotoxic proteins in infectious and allergic diseases, human pDCs were analysed after stimulation with toll-like receptor (TLR)7/9 ligands and in the human asthma model of segmental allergen challenge.Granzyme B (GrB), but not the granzymes A, H, K, M or perforin, was specifically expressed by human pDCs and this GrB expression was up-regulated by IL-3 stimulation. In addition, IL-3-stimulated pDCs were found to kill K562 cells in a GrB- and caspase-dependent manner. TLR7/9 ligands significantly suppressed GrB expression in pDCs. In contrast, there was an up-regulation of GrB in endobronchial pDCs 24 h after allergen challenge, and this was accompanied by enhanced GrB concentrations in bronchoalveolar lavage fluid.We report the selective expression of GrB in human pDCs and show for the first time pDC-mediated GrB- and caspase-dependent cytotoxicity against target cells. In addition, the regulation of GrB expression was investigated in vitro and in vivo providing an evidence for a specific role of pDC-derived GrB in allergic inflammation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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