Abstract
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 CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high 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.
Highlights
Dendritic cells (DCs) are a heterogeneous group of immune cells acting as messengers between the innate and adaptive immune response [1,2,3]
The O-GlcNAc transferase (OGT) level was similar in all three tested cell types, i.e., monocytes, immature monocyte derived dendritic cells (moDCs), mature moDCs, while the expression of OGA was slightly increased in immature moDCs and was twice as high in mature moDCs compared to monocytes
The later somehow contradicts the observed level of O-GlcNAcylated proteins, which was higher in moDCs than in monocytes
Summary
Dendritic cells (DCs) are a heterogeneous group of immune cells acting as messengers between the innate and adaptive immune response [1,2,3]. DCs are able to capture, process and present antigens [4,5,6,7] and in addition to antigen presentation, DCs mediate the appropriate effector or regulatory T cell immune responses by secreting several cytokines, growth factors, and delivering co-stimulatory signals [8,9]. The serine/threonine kinase mammalian target of rapamycin (mTOR) serves as a nutrient sensor It regulates the process of glycolysis, which provides energy for highly demanding processes (e.g., differentiation of DCs) [6,18]. Manipulation of DC signalling pathways could be used to modify immune responses for therapeutic purposes [5,7,24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
