Inhibition of O-GlcNAc transferase alters the differentiation and maturation process of human monocyte derived dendritic cells

Weiss, Matjaž (author), Anderluh, Marko (author), Gobec, Martina (author)

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 OGlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14$^{med}$DC-SIGN$^{low}$HLA-DR$^{med}$CD80$^{low}$CD86$^{high}$ 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.

• Language: English
• Keywords: O-GlcNAcylation, O-GlcNAc transferase (OGT), monocyte derived DCs, OSMI-1, immunometabolism, pharmaceutical chemistry
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 16 str.
• Numbering: Vol. 10, iss. 12, art. 3312
• PID: 20.500.12556/RUL-136702
• UDC: 615.4:54
• ISSN on article: 2073-4409
• DOI: 10.3390/cells10123312
• COBISS.SI-ID: 86685443
• Publication date in RUL: 17.05.2022

Record is a part of a journal

• Title: Cells
• Shortened title: Cells
• Publisher: MDPI
• ISSN: 2073-4409
• COBISS.SI-ID: 519958809

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.12.2021

Secondary language

• Language: Slovenian
• Keywords: farmacevtska kemija, O-GlcNAcilacija, O-GlcNAc transferaza (OGT), DC, pridobljeni iz monocitov, OSMI-1, imunometabolizem

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Young researchers