ISSN  2587-2362  |  E-ISSN  2618-642X
International Journal of Medical Biochemistry The effects of preconditioning with IFN-γ, IL-4, and IL-10 on costimulatory ligand expressions of mesenchymal stem cells [Int J Med Biochem ]
Int J Med Biochem . 2021; 4(2): 121-130 | DOI: 10.14744/ijmb.2021.77487

The effects of preconditioning with IFN-γ, IL-4, and IL-10 on costimulatory ligand expressions of mesenchymal stem cells

Alper Tunga Özdemir1, Mustafa Öztatlici2, Rabia Bilge Özgül Özdemir3, Büşra Çakır4, Kemal Özbilgin2, Ertan Darıverenli5, Cengiz Kirmaz6
1Department of Medical Biochemistry, Merkezefendi State Hospital, Manisa, Turkey
2Department of Histology and Embryology, Manisa Celal Bayar University Faculty of Medicine, Manisa, Turkey
3Department of Allergy and Clinical Immunology, Manisa City Hospital, Manisa, Turkey
4Department of Bioengineering, Ege University Faculty of Engineering, Izmir, Turkey
5Department of Pharmacology, Manisa Celal Bayar University Faculty of Medicine, Manisa, Turkey
6Department of Allergy and Clinical Immunology, Manisa Celal Bayar University Faculty of Medicine, Manisa, Turkey

INTRODUCTION: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells, and co-stimulation may play an important role in increasing the effects of MSCs on adaptive immune cells. Preconditioning may add to the effectiveness of MSCs. The aim of this study was to investigate alterations in the costimulatory ligand expressions of MSCs preconditioned with inflammatory cytokines.
METHODS: MSCs were preconditioned with interferon gamma (IFN-γ), interleukin (IL) 4 (IL-4), and IL-10, and changes in CD80, CD86, CD137L, CD252, CD274, CD275, and human leukocyte antigen (HLA) class I and II expressions were analyzed using flow cytometry and quantitative polymerase chain reaction methods. Human acute monocytic leukemia cell line (THP-1) macrophages preconditioned under the same conditions served as a control for comparison.
RESULTS: The frequencies of CD80 (p=0.0003), CD86 (p<0.0001), CD137L (p<0.0001), CD252 (p=0.0003), CD274 (p=0.0077), CD275 (p<0.0001), and HLA-II (p<0.0001) -positive MSCs was significantly lower than that of the THP-1 macrophages with either method, but there was no significant difference in the HLA-I (p=0.1506) cells. Comparison of the expression of the costimulatory ligands revealed that the expression of MSCs was significantly lower than that of THP-1 cells, and was not affected by cytokine stimuli.
DISCUSSION AND CONCLUSION: The study data indicated that although MSCs are strong immunomodulatory cells, the costimulatory ligand expression required for an effective antigen presentation was extremely low compared with that of professional antigen presenting cells. In addition, preconditioning with IFN-γ, IL-4, and IL-10 failed to increase the expression of important costimulatory ligands, such as CD80 and CD86, in MSCs. The stability of costimulatory ligand expression suggests that MSCs may be an effective source for HLA-I-mediated peripheral tolerance.

Keywords: Costimulatory ligands, interferon gamma, interleukin 4, interleukin 10, mesenchymal stem cells, preconditioning

Alper Tunga Özdemir, Mustafa Öztatlici, Rabia Bilge Özgül Özdemir, Büşra Çakır, Kemal Özbilgin, Ertan Darıverenli, Cengiz Kirmaz. The effects of preconditioning with IFN-γ, IL-4, and IL-10 on costimulatory ligand expressions of mesenchymal stem cells. Int J Med Biochem . 2021; 4(2): 121-130

Corresponding Author: Alper Tunga Özdemir, Türkiye
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