Natural killer (NK) cells play a major role in the initial control of many viral pathogens and in the rejection of tumors. Consistent with their roles as immune sentinels, NK cells are found in inflamed skin, including lichen planus, psoriasis and atopic dermatitis (AD) lesions. In oral lichen planus lesions, the recruitment as well as intradermal colocalization of NK cells and pDC (plasmacytoid dendritic cells) appear to be mediated by chemerin, a recently identified protein ligand for chemokine-like receptor 1 (CMKLR1), a chemoattractant receptor expressed by both cell types. Dendritic cells can regulate NK cell activity, and NK cells can regulate DC-mediated responses. Since chemerin was recently implicated in recruitment of pDC to psoriatic skin, in this work we determined whether chemerin facilitates interactions between NK and pDC in psoriatic plaques through controlling influx of NK cells to diseased skin. We demonstrate that circulating NK cells from normal donors as well as psoriasis and AD patients respond similarly in functional migration assays to chemerin. However, differences in the distribution of NK cells and pDC in skin lesions suggest that recruitment of both NK cells and pDC is unlikely to be controlled solely by chemerin.
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Photopheresis (ECP) is an immunomodulatory therapy that involves extracorporeal exposure of isolated peripheral blood leukocytes to UVA irradiation in the presence of 8-methoxypsoralen (8-MOP) followed by their reinfusion to the patient. However, the underlying mechanism of ECP is not well understood yet. We selected 8-methoxypsoralen (8-MOP), chlorpromazine (CPZ) and 4,6,4'-trimethylangelicine (TMA) because of differences in their ability to induce immune suppression in rats in vivo. In this study, we investigated the role of UVA irradiation of lymphocytes in the presence of TMA, CPZ or 8-MOP on cell apoptosis, and their impact on adhesion of lymphocytes to monocytes in vitro. Apoptosis of lymphocytes and their sub-populations (lymphocytes T and B, NK cells) were determined by a flow cytometry, using AnnexinV-FITC, TUNEL assay and DNA content analysis and antibodies CD3, CD56, CD19. Mitochondrial potential was measured using CMXRos staining and the interaction of monocytes with lymphocytes was monitored by PKH26 Red Sigma staining of lymphocytes and subsequent use of flow cytometry. Our results show a significant increase of apoptosis of the photochemically treated lymphocytes and a decrease of their mitochondrial potential that depended on the dose and time after the treatment. Our data also reveal an increased recognition of apoptotic lymphocytes by freshly isolated monocytes.
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