Uncoupling between CD1d upregulation induced by retinoic acid and conduritol-B-epoxide and iNKT cell responsiveness
| Autor: | Marco Cavallari, Maria Clara Sá Miranda, Andrea Balreira, Fernando A. Arosa |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Retinoic acid Antineoplastic Agents Tretinoin chemical and pharmacologic phenomena Inflammation CD8-Positive T-Lymphocytes Monocytes Cell Line chemistry.chemical_compound Immune system Downregulation and upregulation medicine Humans Immunology and Allergy RNA Messenger Enzyme Inhibitors MHC class II Gaucher Disease Globosides biology Trihexosylceramides Monocyte Histocompatibility Antigens Class II Hematology Molecular biology Coculture Techniques Up-Regulation Hexosaminidases medicine.anatomical_structure chemistry CD1D Chronic Disease biology.protein Natural Killer T-Cells lipids (amino acids peptides and proteins) Antigens CD1d Protein Multimerization medicine.symptom Cell Division Inositol CD8 |
| Zdroj: | Immunobiology. 215:505-513 |
| ISSN: | 0171-2985 |
| DOI: | 10.1016/j.imbio.2009.07.002 |
| Popis: | 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 beta-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(+)Valpha24(+) invariant Natural Killer T (iNKT) cells. In contrast, addition of alpha-galactosylceramide (alpha-GC) induced expansion of Valpha24(+) iNKT cells as determined by using alpha-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. |
| Databáze: | OpenAIRE |
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