# Untangling the role of dopamine release from Tregs: implications for neurodegeneration at the neuron-immune synapse

> **NIH NIH R21** · UNIVERSITY OF CINCINNATI · 2024 · $395,837

## Abstract

PROJECT SUMMARY
A comprehensive understanding of immunity necessitates a thorough exploration of the intricate interactions
between immune cells and neurotransmitters, thereby clarifying their impact on communication at the neuron-
immune synapse. The long-term goal of my research program is to develop new electrochemical and microfluidic
tools to study dynamic neuroimmune communication to understand the molecular mechanisms of
neuroinflammation. To achieve this goal, new approaches are needed which can measure immune cell
communication with higher temporal resolution. The specific objective of this proposal is to demonstrate and
determine the mechanism of subsecond dopamine signaling from CD4+ CD25+ T-cells (Tregs) and to establish
how dopamine release from senescent Tregs impacts neuronal health. Tregs are important immune cells that
function to suppress the immune system and have been implicated in several age-associated neurodegenerative
diseases. Tregs contain the machinery to synthesize and respond to dopamine; however, to date, direct real-time
measurements of dopamine release and how this subsecond signaling influences neuron-immune crosstalk has
not been possible. Current paradigms hold that immune cell secretion of neurotransmitters does not occur with
subsecond dynamics seen in neurons and is therefore dispensable in neuronal biology. The evidence supporting
this viewpoint is limited by the lack of experimental systems to measure physiological secretion of neurotransmitters
by immune cells on this timescale. Our unprecedented preliminary studies using fast-scan cyclic voltammetry
(FSCV) reveals that T cells are capable of rapid subsecond secretion of dopamine. This proposal is based on the
premise that employing traditional neuroscience methods to investigate neurochemical signaling in isolated
immune cells can yield valuable insights into the dynamic mechanisms of subsecond immune cell communication
during aging. The proposal will be completed by the following two specific aims: (1) Ascertain the mechanism of
subsecond dopamine release from Tregs and (2) Develop a neuron-Treg co-culture platform to probe the
consequence of subsecond Treg-derived dopamine signaling on neuronal health with age. We will pursue these
aims with an innovative approach combining the power of FSCV’s subsecond detection capabilities with traditional
immunology approaches in co-cultures of Tregs and cholinergic neurons. This work is significant because we will
reveal the ability of Tregs to release dopamine on a subsecond timescale and demonstrate that this rapid immune-
derived neurochemical signaling influences neuronal health for the first time. The expected outcome is a new
understanding of the dynamics of immune cell signaling and a deeper understanding of the molecular changes
which occur at the neuron-immune cell synapse as a function of age. This work will have a positive impact on how
we study immune cell signaling, and will advance current knowledge o...

## Key facts

- **NIH application ID:** 10866768
- **Project number:** 1R21AG086735-01
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Ashley E Ross
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $395,837
- **Award type:** 1
- **Project period:** 2024-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866768

## Citation

> US National Institutes of Health, RePORTER application 10866768, Untangling the role of dopamine release from Tregs: implications for neurodegeneration at the neuron-immune synapse (1R21AG086735-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10866768. Licensed CC0.

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