cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation

Laban, Kamil G.; Rijken, Rianne; Hiddingh, Sanne; Mertens, Jorre S.; Veen, Rob L. P. van der; Eenhorst, Christine A.E.; Pandit, Aridaman; Radstake, Timothy R. D. J.; Boer, Joke H. de; Kalmann, Rachel; Kuiper, Jonas J.W.

doi:10.1002/eji.201948370

Cited by 9 publications

(8 citation statements)

References 44 publications

(65 reference statements)

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“…Manual gating of data was done using FlowJo software (TreeStar inc San Carlos, CA, USA). FlowSOM v1.18.0 analysis was done as described previously ( Laban et al, 2020 ). Lineage- (negative for CD3/CD56/CD19) HLA-DR+ data were transformed using the logicleTransform function of the flowCore v1.52.1 R package, using default parameters ( Ellis et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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

Hiddingh

Pandit

Verhagen

et al. 2023

eLife

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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 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. 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, an #2021-4). The funders had no role in the design, execution, interpretation, or writing of the study.

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Section: Methodsmentioning

confidence: 99%

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

Hiddingh

Pandit

Verhagen

et al. 2023

eLife

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“…Manual gating of data was done using FlowJo software (TreeStar inc. San Carlos, CA, USA). FlowSOM v1.18.0 ( 41 ) analysis was done as described previously ( 54 ). Lineage- (negative for CD3/CD56/CD19) HLA-DR+ data were transformed using the logicleTransform function of the flowCore v1.52.1 R package, using default parameters ( 55 ).…”

Section: Methodsmentioning

confidence: 99%

“…Manual gating of data was done using FlowJo software (TreeStar inc. San Carlos, CA, USA). FlowSOM v1.18.0 analysis was done as described previously (26).…”

Section: Flow Cytometry Of Cd1c+ DC Populationsmentioning

confidence: 99%

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

Hiddingh

Pandit

Verhagen

et al. 2021

Preprint

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BackgroundInflammatory subsets of CD1c+ conventional dendritic cells (CD1c+ DCs) are promoted by type I interferons (IFN), but the molecular basis for CD1c+ DCs involvement in conditions not driven by type I IFNs is unknown.MethodsOur objective was to use RNA-sequencing of blood CD1c+ DCs and high-dimensional flow cytometry of two cohorts of autoimmune uveitis patients and healthy donors to characterize the CD1c+ DCs population of type I IFN-negative autoimmune uveitis.ResultsWe report that the CD1c+ DCs pool from patients with autoimmune uveitis (n=45) is skewed towards a transcriptional network characterized by surface receptor genes CX3CR1, CCR2, and CD36. We confirmed the association of the transcriptional network with autoimmune uveitis by RNA-sequencing in another case-control cohort (n=35) and demonstrated that this network was governed by NOTCH2-RUNX3 signaling. Unbiased flow cytometry analysis based on the transcriptional network identified blood CD1c+ DC subsets that can be distinguished by CX3CR1 and CD36 surface expression. A CD36+CX3CR1+CD1c+ DC subset within the novel DC3 population was diminished in peripheral blood of patients, while CD1c+ DCs expressing CD36 and CX3CR1 accumulate locally in the inflamed eye. The CD36+CX3CR1+CD1c+ DC subset showed a differential capacity to produce cytokines, including TNF-alpha, IL-6, and VEGF, but not IL-23.ConclusionThese results show that CD1c+ DC subsets defined on the basis of surface expression of CD36 and CX3CR1 are linked to type I IFN-negative human autoimmune uveitis and show a differential capacity to secrete proinflammatory mediators that drive its pathophysiology.Graphical Abstract

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“…Laban et al used flow cytometry to find that the percentages of (HLA-DR+CD303+CD123+) pDCs and (HLA-DR+CD11c+CD1c+) cDCs type-2 in the peripheral blood of OIP patients were significantly lower than those in healthy individuals. Similarly, transcriptome analysis of orbital biopsy showed a reduced abundance of pDC and cDC populations in the OIP microenvironment [ 39 ]. The specific mechanism of the reduction in dendritic cells in OIP is unclear and may be related to etiology.…”

Section: Etiopathogenesismentioning

confidence: 99%

Orbital inflammatory pseudotumor: new advances in diagnosis, pathogenesis, and treatment

Fang,

Shen,

Dai

et al. 2023

Eur J Med Res

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Orbital inflammatory pseudotumor (OIP) is a benign, non-specific inflammatory disorder that commonly occurs in middle-aged adults and is usually unilateral but can occur bilaterally. Its clinical manifestations have tremendous clinical heterogeneity and vary according to the site of infiltration and the degree of lesions, including orbital pain, swelling, diplopia, proptosis, restricted eye movement, and decreased visual acuity. Clinical features, Image characteristics and pathological examinations often need to be evaluated to confirm the diagnosis. Currently, there is no systematic research on the pathogenesis of OIP, which may be related to immunity or infection. The first-line treatment is glucocorticoids. Radiotherapy, immunosuppressants, and biologics can be considered for treatment-resistant, hormone-dependent, or intolerant patients. In this review, we aim to summarize and focus on new insights into OIP, including new diagnostic criteria, pathogenesis, and discoveries in new drugs and treatment strategies. In particular, we highlight the literature and find that T cell-mediated immune responses are closely related to the pathogenesis of OIP. Further exploration of the mechanism and signaling pathway of T cells in the immune process will help to identify their therapeutic targets and carry out targeted therapy to treat refractory OIP and reduce the side effects of traditional treatments.

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cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation

Cited by 9 publications

References 44 publications

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

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

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

Orbital inflammatory pseudotumor: new advances in diagnosis, pathogenesis, and treatment

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