Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under "physiological" hypoxia

• Published in: Immunobiology (1979) Vol. 229; no. 1; p. 152766
• Main Authors: Gornostaeva, A N, Bobyleva, P I, Andreeva, E R, Gogiya, B Sh, Buravkova, L B
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: Adipose-tissue derived mesenchymal stromal cells; Immunosuppression; Cell-to-cell interaction; “Physiological” hypoxia; Differential gene expression
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2023.152766

Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O level. Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or "physiological" hypoxia (5%) O . As revealed with microarray analysis, PBMC transcriptome at 20% O was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O 220 genes were changed. Most of genes at 20% O were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile. Thus, MSC-mediated immunosuppression is executed with greater efficacy at a "physiological" hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.