TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain...

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Autores principales:	David A. Barnes, Dylan A. Galloway, Marius C. Hoener, Mark D. Berry, Craig S. Moore
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	multiple sclerosis trace amines trace amine-associated receptor 1 neuroinflammation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/400c40f3545e4f048a4d3ac2d8e6195f
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spelling	oai:doaj.org-article:400c40f3545e4f048a4d3ac2d8e6195f2021-11-11T17:03:33ZTAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation10.3390/ijms2221115761422-00671661-6596https://doaj.org/article/400c40f3545e4f048a4d3ac2d8e6195f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11576https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.David A. BarnesDylan A. GallowayMarius C. HoenerMark D. BerryCraig S. MooreMDPI AGarticlemultiple sclerosistrace aminestrace amine-associated receptor 1neuroinflammationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11576, p 11576 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multiple sclerosis trace amines trace amine-associated receptor 1 neuroinflammation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	multiple sclerosis trace amines trace amine-associated receptor 1 neuroinflammation Biology (General) QH301-705.5 Chemistry QD1-999 David A. Barnes Dylan A. Galloway Marius C. Hoener Mark D. Berry Craig S. Moore TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
description	TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.
format	article
author	David A. Barnes Dylan A. Galloway Marius C. Hoener Mark D. Berry Craig S. Moore
author_facet	David A. Barnes Dylan A. Galloway Marius C. Hoener Mark D. Berry Craig S. Moore
author_sort	David A. Barnes
title	TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
title_short	TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
title_full	TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
title_fullStr	TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
title_full_unstemmed	TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
title_sort	taar1 expression in human macrophages and brain tissue: a potential novel facet of ms neuroinflammation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/400c40f3545e4f048a4d3ac2d8e6195f
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TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation

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