Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women

Abstract Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on the immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are desc...

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Main Authors: Leonie Fleige, Silvia Capellino
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Biology of Sex Differences
Subjects:
Online Access:https://doi.org/10.1186/s13293-025-00689-5
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author Leonie Fleige
Silvia Capellino
author_facet Leonie Fleige
Silvia Capellino
author_sort Leonie Fleige
collection DOAJ
description Abstract Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on the immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA, and multiplex assays. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions in vitro. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.
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spelling doaj-art-dd8d58f496ab416cae3eaf246fe52c4e2025-02-09T12:04:57ZengBMCBiology of Sex Differences2042-64102025-02-0116111810.1186/s13293-025-00689-5Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in womenLeonie Fleige0Silvia Capellino1Department of Immunology, Research Group of Neuroimmunology, IfADo-Leibniz Research Centre for Working Environment and Human FactorsDepartment of Immunology, Research Group of Neuroimmunology, IfADo-Leibniz Research Centre for Working Environment and Human FactorsAbstract Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on the immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA, and multiplex assays. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions in vitro. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.https://doi.org/10.1186/s13293-025-00689-5DopamineSex-specific differencesHealthy human subjectsMonocytesB cellsCytokines
spellingShingle Leonie Fleige
Silvia Capellino
Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
Biology of Sex Differences
Dopamine
Sex-specific differences
Healthy human subjects
Monocytes
B cells
Cytokines
title Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
title_full Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
title_fullStr Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
title_full_unstemmed Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
title_short Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women
title_sort acute stimulation of pbmcs drives switch from dopamine induced anti to proinflammatory phenotype of monocytes only in women
topic Dopamine
Sex-specific differences
Healthy human subjects
Monocytes
B cells
Cytokines
url https://doi.org/10.1186/s13293-025-00689-5
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