دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis.
المؤلفون: Hiddingh S; Ophthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Pandit A; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Verhagen F; Ophthalmo-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, Netherlands., Rijken R; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Servaas NH; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Wichers RCGK; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Loon NHTD; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Imhof SM; Ophthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Radstake TRDJ; University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands., de Boer JH; Ophthalmo-Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Kuiper JJW; Ophthalmo-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, Netherlands.
المصدر: ELife [Elife] 2023 Apr 12; Vol. 12. Date of Electronic Publication: 2023 Apr 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Transcriptome* , Uveitis*/genetics, Humans ; Antigens, CD1/analysis ; Cytokines ; Dendritic Cells/physiology ; Flow Cytometry ; CX3C Chemokine Receptor 1/genetics
مستخلص: 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.
Competing Interests: SH, AP, FV, RR, NS, RW, NL, SI, Jd, JK No competing interests declared, TR 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
(© 2023, Hiddingh, Pandit, Verhagen et al.)
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فهرسة مساهمة: Keywords: CD1c; RNA-seq; autoimmune response/disease; dendritic cells; human; immunology; inflammation; interferons; medicine; uveitis
سلسلة جزيئية: GEO GSE195501; GSE194060; GSE48590; GSE119242; GSE149619; GSE110577; GSE178833
المشرفين على المادة: 0 (Antigens, CD1)
0 (Cytokines)
0 (CX3CR1 protein, human)
0 (CX3C Chemokine Receptor 1)
تواريخ الأحداث: Date Created: 20230412 Date Completed: 20230517 Latest Revision: 20230524
رمز التحديث: 20230524
مُعرف محوري في PubMed: PMC10185339
DOI: 10.7554/eLife.74913
PMID: 37042831
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.74913