Browsing by Author "Alshomrani, Fatimah Mohammed Saleh"

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Investigating the Impact of IL-17 and IL-4 on Haematopoietic Stem Cells
(Saudi Digital Library, 2023-11-24) Alshomrani, Fatimah Mohammed Saleh; Hewitson, James
Introduction: Haematopoiesis allows blood cells renewal for maintaining blood’s steady-state and stressadapted functioning during infections and inflammations. It is driven by haematopoietic system cells (HSCs) primarily originated at bone marrow. HSCs respond to virus and bacteria-triggered inflammations through altered proliferation and/or differentiation. Little has been known regarding HSCs functioning at type-2 and type-17 immune responses associated with helminths and extracellular fungal infections, respectively. Study aims: We aimed to assess whether specific HSC population (ESLAM) are responsive to IL-17 ± IL-4 and how this could be translated through ESLAM’s proliferation and differentiation. Methods: ESLAM HSCs (lineage- c-kit+ Sca1+ CD48– CD150+ EPCR+) were purified from bone marrow of naïve mice and their proliferation and differentiation -/+ IL-4 and IL-17 were assessed in single cell liquid cultures and bulk colony formation unit (CFU) assays. Results: IL-4 reduced ESLAMs self-renewal through single cell cultures, whereas IL-4 increased ESLAM’s differentiation into megakaryocytes. Only IL-4 altered % differentiated ESLAMs for Ly6C/Ly6G/MHCII markers affecting % monocytes/macrophage lineage. In CFU, IL-4 reduced ESLAM’s colonies which was then partially antagonised on IL-17 co-treatment. ESLAMs’ differentiation was increased with cytokine treatments for Ly6C/Ly6G markers, rather than MHCII, at CD41– CD11b+ subpopulation. Conclusion: cytokines influence ESLAM’s active self-renewal and differentiation with profound activity for IL-4/Th2 over IL- 17/Th17 immune responses. Future work will involve further ESLAM differentiation analysis under interferon-γ, type-1 interferon, and tumour necrosis factor-α, and how their responses would be altered by IL-17 co-treatments. Wider range of ESALM’s
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