Fig. 6: Hypoxia-induced formation of immunoproteasome is responsible for loss of immunoprivilege of MSCs. | Cell Death & Disease

Fig. 6: Hypoxia-induced formation of immunoproteasome is responsible for loss of immunoprivilege of MSCs.

From: Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells

Fig. 6

To determine the immunogenicity of MSCs, normoxic and hypoxic human MSCs (with or without immunoproteasome inhibitor- Onx0914 1 µM for 4 h) were co-cultured with allogeneic leukocytes at a ratio 1:10 for 72 h. a Leukocyte mediated cytotoxicity in MSCs (LDH release) increased significantly in hypoxic MSCs vs. normoxic cells, which was rescued by inhibition of immunoproteasome. n = 5. b The effect of MSCs on leukocyte proliferation was measured using WST1 proliferation assay kit. After 72 h of co-culture, normoxic MSCs were able to decrease leukocyte proliferation compared to control (PHA treated leukocytes). However, hypoxia treated MSCs had no effect on leukocyte proliferation, immunoproteasome inhibited hypoxic MSCs significantly decreased leukocytes proliferation. n = 10. c After 72 h of co-culture, the effect of MSCs on CD4+CD25+FOXP3+ Treg cell induction in a mixed leukocyte population was assessed by flow cytometry. The number of Treg cells decreased after co-culture with hypoxic MSCs. However, co-culture with immunoproteasome inhibited hypoxic MSCs increased the number of Treg cells. n = 3. *p < 0.05 compared to normoxic MSC; @p < 0.05 compared to PHA group; #p < 0.05 compared to hypoxic MSCs, each experiment was repeated 3–4 times.

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