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

Authors :
Fleurieke Verhagen
Aridaman Pandit
Sanne Hiddingh
Rianne Rijken
Nila Hendrika Servaas
Rina CGK Wichers
Ninette H ten Dam-van Loon
Saskia M Imhof
Timothy RDJ Radstake
Joke H de Boer
Jonas JW Kuiper
Source :
eLife. 12
Publication Year :
2023
Publisher :
eLife Sciences Publications, Ltd, 2023.

Abstract

Background: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.Methods: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.Results:We report that the CD1c+ DCs pool from patients with non-infectious uveitis is skewed toward a gene module with the chemokine receptor CX3CR1 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.Conclusions:These results show that CX3CR1+ DC3s are implicated in non-infectious uveitis and can secrete proinflammatory mediators implicated in its pathophysiology.Funding: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.

Details

ISSN :
2050084X
Volume :
12
Database :
OpenAIRE
Journal :
eLife
Accession number :
edsair.doi...........daf43ae95c277ba108546e841817620e