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

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

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.

• Jezik: Angleški jezik
• Ključne besede: O-GlcNAcylation, O-GlcNAc transferase (OGT), monocyte derived DCs, OSMI-1, immunometabolism, pharmaceutical chemistry
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 16 str.
• Številčenje: Vol. 10, iss. 12, art. 3312
• PID: 20.500.12556/RUL-136702
• UDK: 615.4:54
• ISSN pri članku: 2073-4409
• DOI: 10.3390/cells10123312
• COBISS.SI-ID: 86685443
• Datum objave v RUL: 17.05.2022

Gradivo je del revije

• Naslov: Cells
• Skrajšan naslov: Cells
• Založnik: MDPI
• ISSN: 2073-4409
• COBISS.SI-ID: 519958809

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.12.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: farmacevtska kemija, O-GlcNAcilacija, O-GlcNAc transferaza (OGT), DC, pridobljeni iz monocitov, OSMI-1, imunometabolizem

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Program financ.: Young researchers