Trace amine-associated receptor 1 as a novel immunomodulatory target in multiple sclerosis

Barnes, David A. (2022) Trace amine-associated receptor 1 as a novel immunomodulatory target in multiple sclerosis. Masters thesis, Memorial University of Newfoundland.

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Abstract

TAAR1 is a previously established neuroregulator with emerging evidence suggesting a role in modulation of the immune response. Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system (CNS). This study investigated expression of TAAR1 in immune cells relevant to MS pathophysiology in both the periphery and CNS of MS patients. RT-qPCR analyses of TAAR1 mRNA levels in peripheral immune cells from MS patients shared a statistically significant decrease in TAAR1 mRNA in MS patient monocytes compared to controls. TAAR1 expression at the protein-level was visualized in both peripherally-derived and CNS-resident macrophages bordering an MS lesion. Additionally, this study attempted to characterize a function of TAAR1 within the immune system that is relevant to MS neuroinflammation. Effects of TAAR1 agonist treatment on cytokine secretion and on the metabolic profile of pro-inflammatory macrophages from the periphery indicated a potential anti-inflammatory function, however, TAAR1 agonists had no effect on cytokine secretion from macrophages resident to the CNS. This study effectively demonstrates the potential for a novel link between TAAR1 and MS pathophysiology and establishes critical preliminary research towards elucidating the function of TAAR1 in peripheral and CNS-resident macrophages.

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