CD4+ and CD25+ T-cell response to short-time interferon-beta therapy on IL10, IL23A and FOXP3 genes in multiple sclerosis patients
Corresponding Author
Hazal Gezmis
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Department of Materials, University of Oxford, Oxfordshire, OX1 3PH UK
Correspondence
Hazal Gezmis, Department of Medical Biology, Faculty of Medicine, Yeditepe University, 34755, Istanbul, Turkey.
Email: [email protected]
Search for more papers by this authorTansu Doran
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Search for more papers by this authorFusun Mayda Domac
Department of Neurology, University of Health Sciences, Erenkoy Mental and Nervous Diseases Training and Research Hospital, Istanbul, Turkey
Search for more papers by this authorDeniz Yucel
Department of Histology and Embryology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorRahsan Karaci
Department of Neurology, University of Health Sciences, Erenkoy Mental and Nervous Diseases Training and Research Hospital, Istanbul, Turkey
Search for more papers by this authorDeniz Kirac
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Search for more papers by this authorCorresponding Author
Hazal Gezmis
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Department of Materials, University of Oxford, Oxfordshire, OX1 3PH UK
Correspondence
Hazal Gezmis, Department of Medical Biology, Faculty of Medicine, Yeditepe University, 34755, Istanbul, Turkey.
Email: [email protected]
Search for more papers by this authorTansu Doran
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Search for more papers by this authorFusun Mayda Domac
Department of Neurology, University of Health Sciences, Erenkoy Mental and Nervous Diseases Training and Research Hospital, Istanbul, Turkey
Search for more papers by this authorDeniz Yucel
Department of Histology and Embryology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorRahsan Karaci
Department of Neurology, University of Health Sciences, Erenkoy Mental and Nervous Diseases Training and Research Hospital, Istanbul, Turkey
Search for more papers by this authorDeniz Kirac
Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
Search for more papers by this authorHazal Gezmis and Tansu Doran contributed equally to this work.
Abstract
Aim of the Study
Interferon-beta (IFN-β), multiple sclerosis (MS) drug for years, does not have therapeutic effects on each patient. Yet, a considerable portion has experienced no therapeutic response to IFN-β. Therefore, it is necessary to determine disease-specific biomarkers that affect drug response. Here, we aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A), as well as forkhead box P3 (FOXP3) genes on MS after IFN-β therapy.
Materials and Methods
Peripheral blood mononuclear cells (PBMCs) of 42 MS patients were isolated to obtain CD4+ and CD25+ T cells. Both cell types were characterised by flow cytometry. To determine optimum drug concentration of IFN-β, cytotoxicity assays were assessed on each cell type for 4, 16, 24 and 48 hours respectively. Then, cells were cultured in the presence of 500 IU/mL of IFN-β. cDNA synthesis was performed after mRNA extraction. RT-PCR was performed to measure gene expressions of IL10, IL23A and FOXP3. Results were evaluated statistically.
Results
It was found that the cytotoxic effect of IFN-β was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-β. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48 hours in CD4+ T cells. For CD25+ T cells, the graded increase in FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake.
Conclusion
Although a considerable change in expression was obtained, the long-term IFN-β effect on both genes and cells should be determined by follow-up at least a year.
DISCLOSURES
No conflict of interest was declared by the authors.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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