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Survivin; a Novel Therapeutic Target That Correlates With Survival of Autoreactive T Lymphocytes Obtained From Patients With Ankylosing Spondylitis Publisher Pubmed



Shomali N1, 2, 3 ; Baradaran B1, 2 ; Daei Sorkhabi A3 ; Sarkesh A3 ; Saeed Kahrizi M4 ; Tosan F5 ; Mahmoodpoor A6 ; Mardi A7 ; Mohammadi H8, 9 ; Hassanzadeh A10 ; Saeedi H1 ; Hajialilo M11 ; Hemmatzadeh M2 ; Marofi F1 Show All Authors
Authors
  1. Shomali N1, 2, 3
  2. Baradaran B1, 2
  3. Daei Sorkhabi A3
  4. Sarkesh A3
  5. Saeed Kahrizi M4
  6. Tosan F5
  7. Mahmoodpoor A6
  8. Mardi A7
  9. Mohammadi H8, 9
  10. Hassanzadeh A10
  11. Saeedi H1
  12. Hajialilo M11
  13. Hemmatzadeh M2
  14. Marofi F1
  15. Sandoghchian Shotorbani S1, 2
Show Affiliations
Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Surgery, Alborz University of Medical Sciences, Karaj, Iran
  5. 5. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
  6. 6. Department of Anesthesiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  8. 8. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  9. 9. Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  10. 10. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Gene Published:2022


Abstract

Ankylosing spondylitis (AS) is progressive immune-mediated arthritis. Persistent autoreactivity of T cells with an up-regulated Survivin expression is strongly implicated in AS immunopathogenesis. Besides, Survivin can inhibit proapoptotic caspase 9 activations. Moreover, microRNAs are small non-coding RNAs that are dysregulated in various diseases, in which their altered expression could modulate Survivin expression. The primary goal of this study was to assess the role of Survivin and its-targeting microRNAs in the immunopathogenesis of AS disease. For this aim, peripheral blood mononuclear cells (PBMCs) were isolated from 15 patients with AS and healthy matched controls using Ficoll-Hypaque. T cells were obtained using the magnetic-activated cell sorting (MACS) method. After that, the expression levels of Survivin, Caspase 9, and specific miRNAs were determined using qT-qPCR. Also, the expression of Survivin and Caspase 9 at protein levels was determined by western blotting. Then, the isolated T cells were co-cultured with interleukin (IL)-2 and muromonab-CD3 (OKT-3) for active-induced cell death (AICD) induction, Survivin siRNA for inhibition of Survivin expression, and their combination to assess the implication of Survivin expression in autoreactive T lymphocytes' resistance to apoptosis by determining the rate of apoptosis by Flowcytometry assay. The results showed that Survivin was up-regulated while Caspase 9 was downregulated in patients with AS. It was also revealed that microRNAs that directly or indirectly target the Survivin mRNA were dysregulated in patients with AS. It was also revealed that T cells obtained from AS patients were more resistant to apoptosis induction than those obtained from healthy people. In summary, the results obtained from this study showed that dysregulation of Survivin and Survivin-targeting miRNAs in T lymphocytes obtained from AS patients contribute to their resistance to apoptosis, suggesting the future development of targeted therapies for AS. © 2022