Dysregulation of aging regulatory T-cell response in autoimmune disease

Active Project Grant Awarded Last action

Award ID
F31AI200271
Recipient
Awarding agency
Obligated
$38,914

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 0% complete
Place of performance
Salt Lake City, UT 84112, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Autoimmunity is an attack on the self by the immune system, and regulatory T cells (TREGS) play a role in maintaining tolerance to self-antigens. During demyelinating disease, TREGS become a driver of myelin breakdown and disease progression. This process is exacerbated during aging when TREGS are less suppressive than their younger counterparts, leading to more severe disease progression. Our overall goal is to understand the changes that occur in TREGS during aging that led to autoimmune disease. T cell effector function is dictated by a strong interaction via TCR with pmhc from antigen-presenting cells. Weakened interaction between TCR: pmhc could contribute to this tolerance breakdown. This work focuses on the central hypothesis that older individuals have more severe demyelinating disease because of fewer functional TREGS. Diagnosis of demyelinating disease over the age of 50 typically leads to a primary progressive disease pathology for which there are no current treatments. Treg function is dictated via the length of the TCR: pmhc bond lifetime, and our preliminary data show that IT is decreased in aged TREGS. A decrease in bond lifetime could contribute to the decrease in suppressive function we have also seen in aged TREGS. CTLA4 is an inhibitory costimulatory molecule that prevents a secondary signal to prevent T cell activation and is a major regulator of treg suppressive function. Thus, I hypothesize that treg age decreases TCR: pmhc and CTLA4: CD80/86 bond lifetime. My proposal will address the change in treg kinetics leading to dysfunction during aging that can cause autoimmunity. In the following studies, we will test the parameters of treg function in an aged context during a naïve and an autoimmune context. This study will be the first to address the change in treg function during aging based on changing T cell kinetics. We expect to observe diminished functional ability and worsened disease upon completing this project.

Quick answers

Who received award F31AI200271?

F31AI200271 was awarded to University Of Utah by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on November 28, 2026.

How much is award F31AI200271 worth?

$38,914 has been obligated on F31AI200271.

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