Details

Autor(en) / Beteiligte

• Hiddingh, Sanne
• Pandit, Aridaman
• Verhagen, Fleurieke
• Rijken, Rianne
• Servaas, Nila Hendrika
• Wichers, Rina C G K
• Loon, Ninette H Ten Dam-van
• Imhof, Saskia M
• Radstake, Timothy R D J
• de Boer, Joke H
• Kuiper, Jonas J W

Titel

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

Ist Teil von

• eLife, 2023-04, Vol.12

Ort / Verlag

England: eLife Sciences Publications Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Type I interferons (IFNs) promote the expansion of subsets of CD1c+ conventional dendritic cells (CD1c+ DCs), but the molecular basis of CD1c+ DCs involvement in conditions not associated without elevated type I IFNs remains unclear. We analyzed CD1c+ DCs from two cohorts of non-infectious uveitis patients and healthy donors using RNA-sequencing followed by high-dimensional flow cytometry to characterize the CD1c+ DC populations. We report that the CD1c+ DCs pool from patients with non-infectious uveitis is skewed toward a gene module with the chemokine receptor as the key hub gene. We confirmed these results in an independent case-control cohort and show that the disease-associated gene module is not mediated by type I IFNs. An analysis of peripheral blood using flow cytometry revealed that CX3CR1+ DC3s were diminished, whereas CX3CR1- DC3s were not. Stimulated CX3CR1+ DC3s secrete high levels of inflammatory cytokines, including TNF-alpha, and CX3CR1+ DC3 like cells can be detected in inflamed eyes of patients. These results show that CX3CR1+ DC3s are implicated in non-infectious uveitis and can secrete proinflammatory mediators implicated in its pathophysiology. The presented work is supported by UitZicht (project number #2014-4, #2019-10, and #2021-4). The funders had no role in the design, execution, interpretation, or writing of the study.