- Title Information
- Title
- Investigating the Role of V-Immunoglobulin Suppressor of T Cells (VISTA) in the Morbidity and Mortality of Neonatal Sepsis Using a Mouse Model
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Petros, Habesha Fasika
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Chung, Chun-Shiang
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Ayala, Alfred
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Schell, Jacquelyn
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2023
- Physical Description
- Extent
- 5, 33 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2023
- Genre (aat)
- theses
- 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.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00968006")
- Topic
- Immunology
- Subject
- Topic
- Innate immunology
- Subject
- Topic
- Sepsis
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20230602