Pluto Bioinformatics

GSE92852: Generation and functional characterization of MDSC-like cells

Bulk RNA sequencing

Myeloid derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with IL-10 during their differentiation to dendritic cells (moDC) results in the generation of an APC population with a CD14+HLA-DRlow phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Here, we show that co-incubation of IL-10-APC and moDC caused a reduction of DC-induced T cell proliferation, of the expression of maturation markers and of secreted cytokines and chemokines. Furthermore, addition of IL-10-APC increased the immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4 on moDC. Using transcriptome analysis, we could identify a set of molecules and pathways mediating the immunosuppressive effects of IL-10-APCs. In addition, we found that IL-10-APC as well as human isolated MDSC, expressed higher levels of programmed death (PD)-1, PD-ligand-1, glucocorticoid-induced-tumor-necrosis-factor-receptor-related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4, PD-1 or PD-L1 on MDSC using blocking antibodies restored the stimulatory capacity of DC in co-incubation experiments. Our results demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are profoundly involved in the inhibitory effects of MDSC on DC function and might be promising tools for an application in the clinics. SOURCE: Joachim Schultze (j.schultze@uni-bonn.de) - LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)