Description
- Abstract:
- Sepsis - a dysregulated host response to an infection that can lead to life-threatening organ dysfunction - incurs significant health and financial burdens among neonatal populations worldwide. In spite of this, there continues to be a lack of efficacious therapeutics and diagnostics for sepsis. As a result, healthcare providers often resort to non-specific antibiotic treatments and/or source control, while also applying supportive care such as ventilator management, blood glucose maintenance, and other management protocols where organ system dysfunction is evident. The challenges faced with therapeutic and diagnostic developments are linked to the intricate pathogenesis of sepsis that has yet to be fully understood. To better understand this disease, our group investigated the role of a checkpoint protein, V-Domain Ig Suppressor of T-Cell Activation (VISTA), in sepsis. VISTA, among other checkpoint proteins, have been found to be upregulated following sepsis and is predicted to play a role in immunosuppression. In fact, decreased survival and increased serum organ injury markers as well as altered cytokine levels have been reported after a septic insult in VISTA knockout (VISTA-/-) adult mice. However, little is known about the role of checkpoint proteins like VISTA within neonatal populations. To address this gap, our group performed a survival study, organ histology, organ injury assays, inflammatory cytokine assays, and flow cytometry to phenotype immune cell populations in VISTA-/- neonates following a septic insult. The results suggest that VISTA may be playing a role in improving survival and mitigating spleen and liver injury following sepsis in neonates. Additionally, the levels of several serum cytokines (TNF-alpha, IFN gamma, IL-12p70, MCP-1, IL-1 alpha, IL-17a, IL-6, IL-1beta, IL-10) were increased in VISTA -/- groups compared to WT groups after a septic insult. These findings suggest that the role of VISTA in modulating sepsis-induced morbidity and mortality is not only important in adults but also neonatal populations as well.
- Notes:
- Thesis (Sc. M.)--Brown University, 2023
Citation
Petros, Habesha Fasika,
"Investigating the Role of V-Immunoglobulin Suppressor of T Cells (VISTA) in the Morbidity and Mortality of Neonatal Sepsis Using a Mouse Model"
(2023).
Biotechnology, Biology and Medicine Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:f97ywzrn/
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