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+ 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.