Systems Approach to Understanding the Metabolic Regulation of T Cell Phenotype in Autoimmunity
Abstract
Multiple sclerosis (MS) is a debilitating neurological ailment with no available therapies to reverse the disease. With an increasing understanding of immune cell metabolism, there is a renewed clinical interest in implementing dietary interventions to manage autoimmune and other immunological diseases. This warrants a systems-based understanding of the effect of dietary nutrients on gene expression and immune cell function. A group of such nutrients is methyl donors, which affect gene expression and immune cell function. While the effect of dietary methionine restriction has been studied, the role of other metabolites within the methionine/folate cycles and their interplay in directing T cell pathogenicity remain poorly understood. Herein, by combining my expertise in cellular metabolism with my current training in systems immunology, I aim to answer a fundamental question: How does a specific dietary nutrient affect the entire metabolic network of an immune cell to regulate its epigenetics and modulate its function in a particular tissue? The analysis of T cell metabolism in tissue is challenging due to limitations of available cell numbers and current metabolic techniques. Our lab has recently developed a novel computational algorithm called Compass that can predict metabolic changes in immune cells using single cell RNA sequencing data. In the proposed study, we will use a similar approach to integrate transcriptomics (gene expression) and metabolomics of T cells within tissues to generate a holistic map of tissue-specific metabolic alterations resulting from a dietary intervention. This data, in tandem with in vivo perturbation studies on MS disease course, will provide clues to eventually devise dietary interventions for inflammatory and autoimmune diseases. Our proposal aims to address more than one Peer Reviewed Medical Research Program Strategic Goal. While our principal focus is to develop a deeper understanding of nutrition and susceptibility to autoimmune disease, the results of the proposed study will also benefit patients with immunological, neurological, and mitochondrial disorders. Service Members and Veterans have a higher risk of developing immune disorders such as MS. This is exacerbated by limited availability of optimal dietary solutions upon installation and during deployment. With dietary interventions becoming the mainstay of disease management in MS, the outcome of my proposed studies will help develop more than one dietary/therapeutic intervention providing options to Service Members and the general population to manage/prevent immunological diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310120
Entities
People
- Vinee Purohit
Organizations
- United States Army