eLife (Apr 2023)

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

  • Sanne Hiddingh,
  • Aridaman Pandit,
  • Fleurieke Verhagen,
  • 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

DOI
https://doi.org/10.7554/eLife.74913
Journal volume & issue
Vol. 12

Abstract

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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.

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