Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis
- Utrecht University, Netherlands
Abstract
<strong>Background:</strong> 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. <strong>Methods:</strong> 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. <strong>Results:</strong> We report that the CD1c+ DCs pool from patients with non-infectious uveitis is skewed towards 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. <strong>Conclusions:</strong> These results show that CX3CR1+ DC3s are implicated in non-infectious uveitis and can secrete proinflammatory mediators implicated in its pathophysiology. <strong>Funding:</strong> The presented work is supported by UitZicht (project number #2014-4, #2019-10, an #2021-4). The funders had no role in the design, execution, interpretation, or writing of the study.
Data availability
All raw data and data scripts are available via dataverseNL: https://doi.org/10.34894/9Q0FVO and deposited in NCBI's Gene Expression Omnibus accessible through GEO Series accession numbers GSE195501 and GSE194060.
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Article and author information
Author details
Nila Hendrika Servaas
Funding
UitZicht (#2014-4)
- Jonas JW Kuiper
UitZicht (#2019-10)
- Jonas JW Kuiper
UitZicht (#2021-4)
- Jonas JW Kuiper
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: This study was conducted in compliance with the Helsinki principles. Ethical approval was requested and obtained from the Medical Ethical Research Committee in Utrecht. All patients signed written informed consent before participation. (METC protocol number #14-065/M).
Copyright
© 2023, Hiddingh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis
eLife 12:e74913.
https://doi.org/10.7554/eLife.74913
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