کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2183604 1095577 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Uncoupling between CD1d upregulation induced by retinoic acid and conduritol-B-epoxide and iNKT cell responsiveness
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Uncoupling between CD1d upregulation induced by retinoic acid and conduritol-B-epoxide and iNKT cell responsiveness
چکیده انگلیسی

Gaucher disease (GD) is associated with upregulation of CD1d and MHC-class II expression by monocytes. While the physiological impact of CD1d upregulation remains uncertain, it has been proposed that MHC-class II upregulation is associated with inflammation. Hereby, we show that the decrease in MHC-class II expression seen in GD patients under therapy correlates positively with chitotriosidase activity, a marker of inflamed macrophages. We also show that retinoic acid (RA) and the β-glucocerebrosidase inhibitor conduritol-B-epoxide (CBE) lead to upregulation of CD1d expression by THP-1 cells, which correlated with an increase in mRNA expression. In vitro co-culture experiments showed that RA treated THP-1 cells were more stimulatory for CD4+ than for CD8+ T cells, as determined by CFSE loss, in comparison to untreated THP-1 cells. Interestingly, even though addition of exogenous isoglobotrihexosylceramide (iGb3), a physiological CD1d ligand, augmented the percentage of dividing CD4+ T cells, we could not detect a significant expansion of CD4+Vα24+ invariant Natural Killer T (iNKT) cells. In contrast, addition of α-galactosylceramide (α-GC) induced expansion of Vα24+ iNKT cells as determined by using α-GC-loaded human CD1d dimers. These results strengthen the existence of a cross-talk between monocyte lipid accumulation, inflammation and changes in cell surface CD1d and MHC-class II in monocytes, which may result in inappropriate recognition events by immune cells and perpetuate chronic inflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunobiology - Volume 215, Issue 6, June 2010, Pages 505–513
نویسندگان
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