Advisory Committee Chair
Jennifer S Pollock
Advisory Committee Members
Craig L Maynard
Anupam Agarwal
James F George
Robinna G Lorenz
David M Pollock
Document Type
Dissertation
Date of Award
2022
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Homeostatic departure is a central feature across all diseases and disease processes. Currently, the average individual in the US consumes an inordinate quantity of salt. However, it is unclear if only individuals that have proven blood pressure elevation with an acute load of salt should be wary. Here we demonstrate, alongside a growing body of science, that the canonical definition of salt-sensitivity is insufficient. We show that salt-resistant mice demonstrate salt-sensitivity in non-blood pressure focused phenomena, such as the acute activation of CD4+ T cells to mobilize and induce a defective effector cytokine program with high salt. We demonstrate that the homeostatic regulator AHR contributes to sustaining effector T cell stability, and activating AHR provides multi-system benefits, including prevention of hypertension in salt-sensitive mice. Somewhat similarly, individuals with sickle cell disease experience life-long homeostatic instability due to polymer development within their own red blood cells simply due to a single nucleotide polymorphism. In untreated patients, a cascade of events ultimately leads to organ failure and a shortened lifespan. Novel approaches that target the cellular source of endothelin 1, an active participant in maintaining pathology in SCD, provides protection against progression of sickle cell nephropathy, a leading cause of mortality in patients with sickle cell disease. Ultimately, it is imperative to re-establish and sustain homeostasis, whether immunologically or through blood pressure regulation.
Recommended Citation
Molina, Patrick Axel, "Disease and Diet-Induced Disruption of Effector T Cell Homeostasis" (2022). All ETDs from UAB. 359.
https://digitalcommons.library.uab.edu/etd-collection/359
