1. Immunology and Inflammation
  2. Medicine

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

  1. Sanne Hiddingh
  2. Aridaman Pandit
  3. Fleurieke Verhagen
  4. Rianne Rijken
  5. Nila Hendrika Servaas
  6. Rina CGK Wichers
  7. Ninette H ten Dam-van Loon
  8. Saskia S Imhof
  9. Timothy RDJ Radstake
  10. Joke H de Boer
  11. Jonas JW Kuiper  Is a corresponding author
  1. Utrecht University, Netherlands
https://doi.org/10.7554/eLife.74913
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Cite this article
  1. Sanne Hiddingh
  2. Aridaman Pandit
  3. Fleurieke Verhagen
  4. Rianne Rijken
  5. Nila Hendrika Servaas
  6. Rina CGK Wichers
  7. Ninette H ten Dam-van Loon
  8. Saskia S Imhof
  9. Timothy RDJ Radstake
  10. Joke H de Boer
  11. Jonas JW Kuiper
(2023)
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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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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Sanne Hiddingh

    Ophthalmo-Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  2. Aridaman Pandit

    Center for Translational Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2057-9737

  3. Fleurieke Verhagen

    Ophthalmo-Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  4. Rianne Rijken

    Center for Translational Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  5. Nila Hendrika Servaas

    Center for Translational Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9825-7554

  6. Rina CGK Wichers

    Center for Translational Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  7. Ninette H ten Dam-van Loon

    Department of Ophthalmology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  8. Saskia S Imhof

    Ophthalmo-Immunology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  9. Timothy RDJ Radstake

    Department of Ophthalmology, Utrecht University, Utrecht, Netherlands
    Competing interests
    Timothy RDJ Radstake, was a principal investigator in the immune catalyst program of GlaxoSmithKline, which was an independent research program. He did not receive any financial support. Currently, TR is an employee of Abbvie where he holds stock. TR had no part in the design and interpretation of the study results after he started at Abbvie..

  10. Joke H de Boer

    Department of Ophthalmology, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.

  11. Jonas JW Kuiper

    Center for Translational Immunology, Utrecht University, Utrecht, Netherlands
    For correspondence
    j.j.w.kuiper@umcutrecht.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5370-6395

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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  1. Sanne Hiddingh
  2. Aridaman Pandit
  3. Fleurieke Verhagen
  4. Rianne Rijken
  5. Nila Hendrika Servaas
  6. Rina CGK Wichers
  7. Ninette H ten Dam-van Loon
  8. Saskia S Imhof
  9. Timothy RDJ Radstake
  10. Joke H de Boer
  11. Jonas JW Kuiper
(2023)
Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis
eLife 12:e74913.
https://doi.org/10.7554/eLife.74913

Share this article

https://doi.org/10.7554/eLife.74913

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