Mature CD209+CD83+CCR7+ dendritic cells infiltrate the arterial wall in giant cell arteritis and derive from in-situ monocyte differentiation

This study aimed to characterize arterial dendritic cells (DCs) in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Bulk RNA-sequencing, RT-PCR and immunofluorescence analyses were performed from temporal arteries from GCA, PMR and control patients. Public single-cell RNA-seq (scRNA-seq) data on Peripheral Blood Mononuclear Cells (PBMCs) were analyzed from three GCA and three control patients. Bulk RNA-Seq and RT-PCR analyses demonstrated a high level of expression of DC lineage markers (CD209), DC maturation markers (CD83, CCR7) and chemokines associated with DC maturation in GCA arteries. The level of expression of DC lineage and DC maturation associated genes was significantly lower in PMR than in GCA arteries and similar between PMR and control arteries. GCA arteries expressed high levels of GM-CSF and IFNG mRNA. ScRNA-seq analysis of GCA PBMCs demonstrated high expression of IFNGR and CSF2R by classical monocytes and cultures of CD14<sup>+</sup> monocytes with GM-CSF and IFN-γ were able to promote their differentiation into monocyte derived-DCs (mo-DCs). This work provides evidence that mo-DCs infiltrate GCA lesions and could be generated under the influence of GM-CSF and IFN-γ from monocytes infiltrating the arterial wall. Mo-DCs could play an important role in GCA pathogenesis and be targeted by GM-CSF and/or IFN-γ inhibitors.

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Publication Details

Journal
Scientific Reports
Published
2025-10-17
DOI
https://doi.org/10.1038/s41598-025-20436-5
Primary Topic
Vasculitis and related conditions
Type
article
Field-Weighted Citation Impact
0.00

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article

Mature CD209+CD83+CCR7+ dendritic cells infiltrate the arterial wall in giant cell arteritis and derive from in-situ monocyte differentiation

Corentin Richard, Paul Ornetti, Coraline Genet, M. Samson et al.
Scientific Reports
Vasculitis and related conditions
article

Mature CD209+CD83+CCR7+ dendritic cells infiltrate the arterial wall in giant cell arteritis and derive from in-situ monocyte differentiation

Corentin Richard, Paul Ornetti, Coraline Genet, M. Samson, Nathalie Klopfenstein, Claudie Cladière, Hélène Greigert, Roman Praliaud, Louis Arnould, Sylvain Audia, Pierre‐Henry Gabrielle, Romain Boidot, Jean-Françis Maillefert, Baptiste Lamarthée, Georges Tarris, Laurent Martin, G. Brenac, André Ramon, Marion Ciudad, Bernard Bonnotte, Alexis Varin, Catherine Creuzot Garcher
article en

Abstract

This study aimed to characterize arterial dendritic cells (DCs) in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Bulk RNA-sequencing, RT-PCR and immunofluorescence analyses were performed from temporal arteries from GCA, PMR and control patients. Public single-cell RNA-seq (scRNA-seq) data on Peripheral Blood Mononuclear Cells (PBMCs) were analyzed from three GCA and three control patients. Bulk RNA-Seq and RT-PCR analyses demonstrated a high level of expression of DC lineage markers (CD209), DC maturation markers (CD83, CCR7) and chemokines associated with DC maturation in GCA arteries. The level of expression of DC lineage and DC maturation associated genes was significantly lower in PMR than in GCA arteries and similar between PMR and control arteries. GCA arteries expressed high levels of GM-CSF and IFNG mRNA. ScRNA-seq analysis of GCA PBMCs demonstrated high expression of IFNGR and CSF2R by classical monocytes and cultures of CD14<sup>+</sup> monocytes with GM-CSF and IFN-γ were able to promote their differentiation into monocyte derived-DCs (mo-DCs). This work provides evidence that mo-DCs infiltrate GCA lesions and could be generated under the influence of GM-CSF and IFN-γ from monocytes infiltrating the arterial wall. Mo-DCs could play an important role in GCA pathogenesis and be targeted by GM-CSF and/or IFN-γ inhibitors.

Scientific ReportsVol. 15(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Bourgogne (FR), Centre Hospitalier Universitaire de Besançon (FR), Centre Georges François Leclerc (FR), CHU Dijon Bourgogne (FR), Maison des Sciences sociales et des Humanités de Dijon (FR), Université de Franche-Comté (FR)
Université de Bourgogne, Direction Générale de l’offre de Soins
Openalex Percentile: Top 58%
Vasculitis and related conditions
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