Zarina Brune

Feinstein Institutes for Medical Research
Project Title: A novel role for IRF5 in CD4+ T cell metabolism drives autoimmunity
Mentor: Betsy Barnes, PhD Investigator Head, Laboratory of Autoimmune and Cancer Research Professor, Departments of Molecular Medicine and Pediatrics

Project Summary: Lupus is a devastating disease where your immune system, normally in charge of defending you from infection, begins to attack your own cells. Patients with lupus can suffer damage to nearly every organ in their body. Unfortunately, the available treatments are associated with dangerous and sometimes deadly side effects.

We believe that T cell dysregulation is a driver of lupus disease. T cells normally recognize invaders and organize the body’s defenses by initiating a specific inflammatory response. However, studies have shown that regulation of T cell responses is disrupted in lupus. Patients have increased T cells associated with inflammation even when no pathogen is present.

Data in our lab has led us to believe that altered T cell metabolism is driving this dysregulation. Metabolism is a process used by every cell to generate the building blocks necessary for survival. In T cells this process is highly linked to their specific response to foreign invaders. Studies show that the imbalance in lupus T cell response is highly linked to dysregulated T cell metabolism.

Our studies specifically focus on clarifying the role of Interferon Regulatory Factor 5 (IRF5) in T cell metabolic programming. Patients with lupus often have increased activity and/or levels of IRF5 in their immune cells.

T cells from lupus patients also exhibit increased metabolism. Interestingly, experiments in mouse models have shown that removing Irf5 protects mice from developing lupus. Our lab has shown that loss of Irf5 decreases metabolic pathway activation in murine T cells.

Determining how IRF5 regulates T cell metabolism is a significant step towards identifying drug development targets. Studies demonstrate that reprogramming T cell metabolism is a key step in either causing or reversing autoimmune disease.

Our findings will shed light on novel pathways that are dysregulated in lupus T cells which, if targeted properly, may offer innovative effective and specific lupus therapeutics.