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

S. Hiddingh; A. Pandit; F. H. Verhagen; R. Rijken; N. H. Servaas; C. G.K. Wichers; N. H. Ten Dam-Van Loon; S. M. Imhof; T. R.D.J. Radstake; J. H. de Boer; J. J.W. Kuiper

doi:10.7554/eLife.74913

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

S. Hiddingh, A. Pandit, F. H. Verhagen, R. Rijken, N. H. Servaas, C. G.K. Wichers, N. H. Ten Dam-Van Loon, S. M. Imhof, T. R.D.J. Radstake, J. H. de Boer, J. J.W. Kuiper^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	e74913
Journal	eLife
Volume	12
DOIs	https://doi.org/10.7554/eLife.74913
Publication status	Published - 12 Apr 2023

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elife-74913-v2Final published version, 1.83 MBLicence: CC BY

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@article{1aae00052aca47889317b582647fa0c7,

title = "Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis",

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.",

author = "S. Hiddingh and A. Pandit and Verhagen, {F. H.} and R. Rijken and Servaas, {N. H.} and Wichers, {C. G.K.} and {Ten Dam-Van Loon}, {N. H.} and Imhof, {S. M.} and Radstake, {T. R.D.J.} and {de Boer}, {J. H.} and Kuiper, {J. J.W.}",

note = "Publisher Copyright: {\textcopyright} 2023, Hiddingh, Pandit, Verhagen et al.",

year = "2023",

month = apr,

day = "12",

doi = "10.7554/eLife.74913",

language = "English",

volume = "12",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

AU - Hiddingh, S.

AU - Pandit, A.

AU - Verhagen, F. H.

AU - Rijken, R.

AU - Servaas, N. H.

AU - Wichers, C. G.K.

AU - Ten Dam-Van Loon, N. H.

AU - Imhof, S. M.

AU - Radstake, T. R.D.J.

AU - de Boer, J. H.

AU - Kuiper, J. J.W.

PY - 2023/4/12

Y1 - 2023/4/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85158003560&partnerID=8YFLogxK

U2 - 10.7554/eLife.74913

DO - 10.7554/eLife.74913

M3 - Article

C2 - 37042831

AN - SCOPUS:85158003560

SN - 2050-084X

VL - 12

JO - eLife

JF - eLife

M1 - e74913

ER -

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

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