Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/74913 |
| _version_ | 1797826647788879872 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sanne Hiddingh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T12:35:46Z |
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| id | doaj.art-c7ecdc3eeef548b1be8313533ffd3d17 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T12:35:46Z |
| publishDate | 2023-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c7ecdc3eeef548b1be8313533ffd3d172023-05-15T14:20:55ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.74913Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitisSanne Hiddingh0Aridaman Pandit1https://orcid.org/0000-0003-2057-9737Fleurieke Verhagen2Rianne Rijken3Nila Hendrika Servaas4https://orcid.org/0000-0002-9825-7554Rina CGK Wichers5Ninette H ten Dam-van Loon6Saskia M Imhof7Timothy RDJ Radstake8Joke H de Boer9Jonas JW Kuiper10https://orcid.org/0000-0002-5370-6395Ophthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsOphthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsOphthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsUniversity Medical Center Utrecht and Utrecht University, Utrecht, NetherlandsOphthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsOphthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsBackground: 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.https://elifesciences.org/articles/74913dendritic cellsautoimmune response/diseaseuveitisCD1cRNA-seqinterferons |
| spellingShingle | 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 Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis eLife dendritic cells autoimmune response/disease uveitis CD1c RNA-seq interferons |
| title | Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis |
| title_full | Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis |
| title_fullStr | Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis |
| title_full_unstemmed | Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis |
| title_short | Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis |
| title_sort | transcriptome network analysis implicates cx3cr1 positive type 3 dendritic cells in non infectious uveitis |
| topic | dendritic cells autoimmune response/disease uveitis CD1c RNA-seq interferons |
| url | https://elifesciences.org/articles/74913 |
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