Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells
The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte de...
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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3312 |
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| author | Matjaž Weiss Marko Anderluh Martina Gobec |
| author_facet | Matjaž Weiss Marko Anderluh Martina Gobec |
| author_sort | Matjaž Weiss |
| collection | DOAJ |
| description | The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14<sup>med</sup>DC-SIGN<sup>low</sup>HLA-DR<sup>med</sup>CD80<sup>low</sup>CD86<sup>high</sup> profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions. |
| first_indexed | 2024-03-10T04:25:26Z |
| format | Article |
| id | doaj.art-0e5f3da796b948ec9dd1a3c07211b04a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:25:26Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0e5f3da796b948ec9dd1a3c07211b04a2023-11-23T07:36:08ZengMDPI AGCells2073-44092021-11-011012331210.3390/cells10123312Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic CellsMatjaž Weiss0Marko Anderluh1Martina Gobec2The Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, SloveniaThe Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, SloveniaThe Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, SloveniaThe O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14<sup>med</sup>DC-SIGN<sup>low</sup>HLA-DR<sup>med</sup>CD80<sup>low</sup>CD86<sup>high</sup> profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.https://www.mdpi.com/2073-4409/10/12/3312O-GlcNAcylationO-GlcNAc transferase (OGT)monocyte derived DCsOSMI-1immunometabolismOSMI-1 |
| spellingShingle | Matjaž Weiss Marko Anderluh Martina Gobec Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells Cells O-GlcNAcylation O-GlcNAc transferase (OGT) monocyte derived DCs OSMI-1 immunometabolism OSMI-1 |
| title | Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells |
| title_full | Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells |
| title_fullStr | Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells |
| title_full_unstemmed | Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells |
| title_short | Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells |
| title_sort | inhibition of o glcnac transferase alters the differentiation and maturation process of human monocyte derived dendritic cells |
| topic | O-GlcNAcylation O-GlcNAc transferase (OGT) monocyte derived DCs OSMI-1 immunometabolism OSMI-1 |
| url | https://www.mdpi.com/2073-4409/10/12/3312 |
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