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Olfactory receptors in macrophages and inflammation

Olfactory receptors (ORs) that bind odorous ligands are the largest family of G-protein-coupled receptors. In the olfactory epithelium, approximately 400 and 1,100 members are expressed in humans and mice, respectively. Growing evidence suggests the extranasal functions of ORs. Here, we review OR ex...

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Autores principales: Orecchioni, Marco, Matsunami, Hiroaki, Ley, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606742/
https://www.ncbi.nlm.nih.gov/pubmed/36311776
http://dx.doi.org/10.3389/fimmu.2022.1029244
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author Orecchioni, Marco
Matsunami, Hiroaki
Ley, Klaus
author_facet Orecchioni, Marco
Matsunami, Hiroaki
Ley, Klaus
author_sort Orecchioni, Marco
collection PubMed
description Olfactory receptors (ORs) that bind odorous ligands are the largest family of G-protein-coupled receptors. In the olfactory epithelium, approximately 400 and 1,100 members are expressed in humans and mice, respectively. Growing evidence suggests the extranasal functions of ORs. Here, we review OR expression and function in macrophages, specialized innate immune cells involved in the detection, phagocytosis, and destruction of cellular debris and pathogens as well as the initiation of inflammatory responses. RNA sequencing data in mice suggest that up to 580 ORs may be expressed in macrophages. Macrophage OR expression is increased after treatment with the Toll-like receptor 4 ligand lipopolysaccharide, which also induces the transcription of inflammasome components. Triggering human OR6A2 or its mouse orthologue Olfr2 with their cognate ligand octanal induces inflammasome assembly and the secretion of IL-1β, which exacerbates atherosclerosis. Octanal is positively correlated with blood lipids like low-density lipoprotein –cholesterol in humans. Another OR, Olfr78, is activated by lactate, which promotes the generation of tumor-associated macrophages that dampen the immune response and promote tumor progression. Olfactory receptors in macrophages are a rich source of untapped opportunity for modulating inflammation. It is not known which of the many ORs expressed in macrophages promote or modulate inflammation. Progress in this area also requires deorphanizing more ORs and determining the sources of their ligands.
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spelling pubmed-96067422022-10-28 Olfactory receptors in macrophages and inflammation Orecchioni, Marco Matsunami, Hiroaki Ley, Klaus Front Immunol Immunology Olfactory receptors (ORs) that bind odorous ligands are the largest family of G-protein-coupled receptors. In the olfactory epithelium, approximately 400 and 1,100 members are expressed in humans and mice, respectively. Growing evidence suggests the extranasal functions of ORs. Here, we review OR expression and function in macrophages, specialized innate immune cells involved in the detection, phagocytosis, and destruction of cellular debris and pathogens as well as the initiation of inflammatory responses. RNA sequencing data in mice suggest that up to 580 ORs may be expressed in macrophages. Macrophage OR expression is increased after treatment with the Toll-like receptor 4 ligand lipopolysaccharide, which also induces the transcription of inflammasome components. Triggering human OR6A2 or its mouse orthologue Olfr2 with their cognate ligand octanal induces inflammasome assembly and the secretion of IL-1β, which exacerbates atherosclerosis. Octanal is positively correlated with blood lipids like low-density lipoprotein –cholesterol in humans. Another OR, Olfr78, is activated by lactate, which promotes the generation of tumor-associated macrophages that dampen the immune response and promote tumor progression. Olfactory receptors in macrophages are a rich source of untapped opportunity for modulating inflammation. It is not known which of the many ORs expressed in macrophages promote or modulate inflammation. Progress in this area also requires deorphanizing more ORs and determining the sources of their ligands. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9606742/ /pubmed/36311776 http://dx.doi.org/10.3389/fimmu.2022.1029244 Text en Copyright © 2022 Orecchioni, Matsunami and Ley https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Orecchioni, Marco
Matsunami, Hiroaki
Ley, Klaus
Olfactory receptors in macrophages and inflammation
title Olfactory receptors in macrophages and inflammation
title_full Olfactory receptors in macrophages and inflammation
title_fullStr Olfactory receptors in macrophages and inflammation
title_full_unstemmed Olfactory receptors in macrophages and inflammation
title_short Olfactory receptors in macrophages and inflammation
title_sort olfactory receptors in macrophages and inflammation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606742/
https://www.ncbi.nlm.nih.gov/pubmed/36311776
http://dx.doi.org/10.3389/fimmu.2022.1029244
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