Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis

Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendrit...

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Autores principales: Sinner, Pia, Peckert-Maier, Katrin, Mohammadian, Hashem, Kuhnt, Christine, Draßner, Christina, Panagiotakopoulou, Vasiliki, Rauber, Simon, Linnerbauer, Mathias, Haimon, Zhana, Royzman, Dmytro, Kronenberg-Versteeg, Deborah, Ramming, Andreas, Steinkasserer, Alexander, Wild, Andreas B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394088/
https://www.ncbi.nlm.nih.gov/pubmed/37528070
http://dx.doi.org/10.1038/s41467-023-40370-2
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author Sinner, Pia
Peckert-Maier, Katrin
Mohammadian, Hashem
Kuhnt, Christine
Draßner, Christina
Panagiotakopoulou, Vasiliki
Rauber, Simon
Linnerbauer, Mathias
Haimon, Zhana
Royzman, Dmytro
Kronenberg-Versteeg, Deborah
Ramming, Andreas
Steinkasserer, Alexander
Wild, Andreas B.
author_facet Sinner, Pia
Peckert-Maier, Katrin
Mohammadian, Hashem
Kuhnt, Christine
Draßner, Christina
Panagiotakopoulou, Vasiliki
Rauber, Simon
Linnerbauer, Mathias
Haimon, Zhana
Royzman, Dmytro
Kronenberg-Versteeg, Deborah
Ramming, Andreas
Steinkasserer, Alexander
Wild, Andreas B.
author_sort Sinner, Pia
collection PubMed
description Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendritic cells and macrophages. Although the expression of CD83 is associated with early microglia activation in various disease settings, its functional relevance for microglial biology has been elusive. Here, we describe a thorough assessment of CD83 regulation in microglia and show that CD83 expression in murine microglia is not only associated with cellular activation but also with pro-resolving functions. Using single-cell RNA-sequencing, we reveal that conditional deletion of CD83 results in an over-activated state during neuroinflammation in the experimental autoimmune encephalomyelitis model. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system, deteriorating resolving mechanisms and exacerbating the disease. Thus, CD83 in murine microglia orchestrates cellular activation and, consequently, also the resolution of neuroinflammation.
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spelling pubmed-103940882023-08-03 Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis Sinner, Pia Peckert-Maier, Katrin Mohammadian, Hashem Kuhnt, Christine Draßner, Christina Panagiotakopoulou, Vasiliki Rauber, Simon Linnerbauer, Mathias Haimon, Zhana Royzman, Dmytro Kronenberg-Versteeg, Deborah Ramming, Andreas Steinkasserer, Alexander Wild, Andreas B. Nat Commun Article Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendritic cells and macrophages. Although the expression of CD83 is associated with early microglia activation in various disease settings, its functional relevance for microglial biology has been elusive. Here, we describe a thorough assessment of CD83 regulation in microglia and show that CD83 expression in murine microglia is not only associated with cellular activation but also with pro-resolving functions. Using single-cell RNA-sequencing, we reveal that conditional deletion of CD83 results in an over-activated state during neuroinflammation in the experimental autoimmune encephalomyelitis model. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system, deteriorating resolving mechanisms and exacerbating the disease. Thus, CD83 in murine microglia orchestrates cellular activation and, consequently, also the resolution of neuroinflammation. Nature Publishing Group UK 2023-08-01 /pmc/articles/PMC10394088/ /pubmed/37528070 http://dx.doi.org/10.1038/s41467-023-40370-2 Text en © The Author(s) 2023 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sinner, Pia
Peckert-Maier, Katrin
Mohammadian, Hashem
Kuhnt, Christine
Draßner, Christina
Panagiotakopoulou, Vasiliki
Rauber, Simon
Linnerbauer, Mathias
Haimon, Zhana
Royzman, Dmytro
Kronenberg-Versteeg, Deborah
Ramming, Andreas
Steinkasserer, Alexander
Wild, Andreas B.
Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title_full Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title_fullStr Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title_full_unstemmed Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title_short Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
title_sort microglial expression of cd83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394088/
https://www.ncbi.nlm.nih.gov/pubmed/37528070
http://dx.doi.org/10.1038/s41467-023-40370-2
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