Biology of the dopamine transporter on human macrophages

Abstract

Neuromodulators, such as norepinephrine and dopamine, regulate immune responses. In addition to receptor competency, select immune cells express machinery to engage in active neurotransmitter transmission. Specifically, macrophages express the norepinephrine (NET) and dopamine transporters (DAT). However, how these transporters - classically studied in central neurons - affect immunity remains poorly understood. To this end, we investigated the expression and function of NET and DAT in human macrophages. We found that monocyte-derived macrophages express functional NET and DAT in vitro. A subset of human intestinal macrophages were further confirmed to express DAT in situ. Interestingly, we discovered that inhibiting DAT, but not NET, enhanced the pro-inflammatory macrophage program in response to an immune challenge. We attribute this modulation to an observed LPS-induced efflux of dopamine through DAT that engages an autocrine dopamine signaling loop. Collectively, we propose that DAT actively regulates dopamine signaling on immune cells, and, in this context, DAT on macrophages is a novel, dynamic immunomodulator.