The modulation effect of inflammatory cytokines on T cell proliferation in hypertension

Alsheik, Eman Oboud S. (2024) The modulation effect of inflammatory cytokines on T cell proliferation in hypertension. PhD thesis, University of Glasgow.

Abstract

Hypertension is a common medical condition with very serious target organ consequences, increasing the risk of heart disease, stroke, and severe health complications. Despite the identification of various mechanisms (vascular, renal, and central mechanism) contributing to the pathogenesis of hypertension, the majority of cases lack a clear aetiology. Emerging evidence has established a significant association between hypertension and immune responses, particularly involving adaptive immune cells and inflammatory cytokines. Immunosuppressive drugs and cytokine inhibitors have shown potential in mitigating hypertension, suggesting a crucial role of the immune system in this condition. Given the central role of T lymphocytes in the adaptive immune response, this study hypothesises that, in the context of hypertension, inflammatory cytokines can modulate T cell activation independently of antigen stimulation. To test this hypothesis, total T cells were isolated from the spleens and PBMCs of normotensive and hypertensive mice and exposed to a range of cytokines, including TNF-α, IL-6, IL-15, IFN-γ, IL-7, IL-1β, IL-17A, IL-2, and IL-12, using different stimulation protocols. Aiming to understand the effects of these cytokines on T cell proliferation, differentiation, and the expression of activation markers such as CD69.

Our findings highlight the varying abilities of cytokines to sustain T cell viability, with IL7, IL-15, and IL-6 demonstrating a tendency for greater efficacy compared to other cytokines. In addition, IL-7 and IL-15 significantly impact T cell proliferation, notably affecting the CD8+ T cell population. However, despite these effects, no significant difference was detected between normotensive and hypertensive T cells in response to IL-7 and IL-15. This suggests that while these cytokines are potent in driving T cell proliferation, their influence is not specifically heightened in the context of hypertension. In GSEA and KEGG analyses, the Ca2+ signalling pathway was distinctively activated in response to IL-7 and IL-15 in Ang II induced hypertension.

Conclusion: These data imply that most studied cytokines linked to hypertension pathology do not substantially affect normotensive or hypertensive T cells in a murine model. However, T cell proliferation was elevated in both Sham and Ang II mice in response to IL-15 and IL-7. Together, the data presented in this thesis warrant further investigations into the role of cytokines in hypertension and may point to IL-15 or IL-7 as biological targets for antihypertension therapy.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from the University of Umm AlQura and the Royal Embassy of Saudi Arabia (Cultural Bureau).
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Supervisor's Name: Czesnikiewicz-Guzik, Dr. Marta and Guzik, Professor Tomasz
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84673
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 08 Nov 2024 12:26
• Last Modified: 08 Nov 2024 12:26
• Thesis DOI: 10.5525/gla.thesis.84673
• URI: https://theses.gla.ac.uk/id/eprint/84673