期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 92, 期 12, 页码 1293-1304出版社
SPRINGER
DOI: 10.1007/s00109-014-1200-z
关键词
Cystic fibrosis; HLA-DQ; HLA-DR; Inflammation; Monocytes, macrophages and dendritic cells
We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) and mRNA level (RT-PCR) in adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (Delta MnI) on classical blood monocytes. In F508del homozygous CF patients, the average Delta MnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 Delta MnI (average 3.25 Delta MnI, CF-DQ(group1)) and 36 below (average 1.24 Delta MnI, CF-DQ(group2)). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQ(group2) patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQ(group2). MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQ beta 1 for CF-DQ(group2) patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide reduced HLA-DQ expression. Interferon gamma (IFN gamma) could overcome this effect in healthy donor cells while, in CF, the IFN gamma-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA-DQ expression in CF, which is associated with inflammation and a reduced response to IFN gamma. aEuro cent CF patients show a reduced expression of MHCII molecules in monocytes and macrophages. aEuro cent HLA-DQ and HLA-DR transcript levels are also reduced in CF patients. aEuro cent CF patient C-reactive protein levels correlate with low HLA-DQ expression. aEuro cent Reduced expression of MHC class II molecules appears to be linked to inflammation. aEuro cent CF patients exhibit an impaired response to IFNgamma.
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