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Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients

Neuroinflammation, in which activated microglia are involved, appears to contribute to the development of Parkinson’s disease (PD). However, the role of microglial activation and the mechanisms governing this process remain uncertain. We focused on one inhibitory mechanism involved in the control of...

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Autores principales: Rabaneda-Lombarte, Neus, Vidal-Taboada, José Manuel, Valente, Tony, Ezquerra, Mario, Fernández-Santiago, Rubén, Martí, María José, Compta, Yaroslau, Saura, Josep, Solà, Carme
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927151/
https://www.ncbi.nlm.nih.gov/pubmed/35296683
http://dx.doi.org/10.1038/s41531-022-00290-2
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author Rabaneda-Lombarte, Neus
Vidal-Taboada, José Manuel
Valente, Tony
Ezquerra, Mario
Fernández-Santiago, Rubén
Martí, María José
Compta, Yaroslau
Saura, Josep
Solà, Carme
author_facet Rabaneda-Lombarte, Neus
Vidal-Taboada, José Manuel
Valente, Tony
Ezquerra, Mario
Fernández-Santiago, Rubén
Martí, María José
Compta, Yaroslau
Saura, Josep
Solà, Carme
author_sort Rabaneda-Lombarte, Neus
collection PubMed
description Neuroinflammation, in which activated microglia are involved, appears to contribute to the development of Parkinson’s disease (PD). However, the role of microglial activation and the mechanisms governing this process remain uncertain. We focused on one inhibitory mechanism involved in the control of microglial activation, the microglia inhibitory receptor CD200R1, and its ligand CD200, mainly expressed by neurons. The human CD200R1 gene encodes two membrane-associated and two soluble protein isoforms and the human CD200 gene encodes full-length proteins (CD200full) but also truncated (CD200tr) proteins which act as CD200R1 antagonists. Little is known about their expression in the human brain under pathological conditions. We used human peripheral blood monocytes and monocyte-derived microglia-like cells from control subjects to characterize the expression of the CD200R1 mRNA variants, which showed stimulus-specific responses. We provide evidence of increased CD200R1 (mRNA variants and protein isoforms) and CD200 expression (CD200tr mRNA) in brain tissue of PD patients, mainly in the hippocampus, as well as increased CD200 expression (CD200full and CD200tr mRNAs) in iPSCs-derived dopaminergic neurons generated from skin fibroblasts of PD patients. Our results suggest that CD200-CD200R1 signalling is altered in PD, which may affect the microglial function and constitute a potential target in therapeutic strategies for PD.
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spelling pubmed-89271512022-04-01 Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients Rabaneda-Lombarte, Neus Vidal-Taboada, José Manuel Valente, Tony Ezquerra, Mario Fernández-Santiago, Rubén Martí, María José Compta, Yaroslau Saura, Josep Solà, Carme NPJ Parkinsons Dis Article Neuroinflammation, in which activated microglia are involved, appears to contribute to the development of Parkinson’s disease (PD). However, the role of microglial activation and the mechanisms governing this process remain uncertain. We focused on one inhibitory mechanism involved in the control of microglial activation, the microglia inhibitory receptor CD200R1, and its ligand CD200, mainly expressed by neurons. The human CD200R1 gene encodes two membrane-associated and two soluble protein isoforms and the human CD200 gene encodes full-length proteins (CD200full) but also truncated (CD200tr) proteins which act as CD200R1 antagonists. Little is known about their expression in the human brain under pathological conditions. We used human peripheral blood monocytes and monocyte-derived microglia-like cells from control subjects to characterize the expression of the CD200R1 mRNA variants, which showed stimulus-specific responses. We provide evidence of increased CD200R1 (mRNA variants and protein isoforms) and CD200 expression (CD200tr mRNA) in brain tissue of PD patients, mainly in the hippocampus, as well as increased CD200 expression (CD200full and CD200tr mRNAs) in iPSCs-derived dopaminergic neurons generated from skin fibroblasts of PD patients. Our results suggest that CD200-CD200R1 signalling is altered in PD, which may affect the microglial function and constitute a potential target in therapeutic strategies for PD. Nature Publishing Group UK 2022-03-16 /pmc/articles/PMC8927151/ /pubmed/35296683 http://dx.doi.org/10.1038/s41531-022-00290-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rabaneda-Lombarte, Neus
Vidal-Taboada, José Manuel
Valente, Tony
Ezquerra, Mario
Fernández-Santiago, Rubén
Martí, María José
Compta, Yaroslau
Saura, Josep
Solà, Carme
Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title_full Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title_fullStr Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title_full_unstemmed Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title_short Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson’s disease patients
title_sort altered expression of the immunoregulatory ligand-receptor pair cd200-cd200r1 in the brain of parkinson’s disease patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927151/
https://www.ncbi.nlm.nih.gov/pubmed/35296683
http://dx.doi.org/10.1038/s41531-022-00290-2
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