Dendritic Cells in Systemic Lupus Erythematosus: From Pathogenic Players to Therapeutic Tools

Klarquist, Jared; Zhou, Zhenyuan; Shen, Nan; Janssen, Edith M.

doi:10.1155/2016/5045248

Cited by 50 publications

(34 citation statements)

References 143 publications

(131 reference statements)

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“…The role of pDCs in cancer is supported by the observation of pDC restoration in peripheral blood in patients under anticancer treatment . In contrast to pDC associated conditions such as primary Sjögren's syndrome and systemic sclerosis that show accumulation of pDCs at the side of inflammation , we observed a moderate decrease in the estimated pDC numbers in biopsies. Here, it is important to consider that it was previously found that pDCs in mice can be segregated into multiple populations with functional differences.…”

Section: Discussionsupporting

confidence: 56%

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

et al. 2020

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Non‐Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology. To investigate the immune cell composition of these diseases, we performed standardized 29 parameter flow cytometry phenotyping in peripheral blood mononuclear cells of 18 NHOL patients, 21 IOI patients, and 41 unaffected controls. Automatic gating by FlowSOM revealed decreased abundance of meta‐clusters containing dendritic cells in patients, which we confirmed by manual gating. A decreased percentage of (HLA‐DR+CD303+CD123+) plasmacytoid dendritic cells (pDC) in the circulation of IOI patients and decreased (HLA‐DR+CD11c+CD1c+) conventional dendritic cells (cDC) type‐2 for IOI patients were replicated in an independent cohort of patients and controls. Meta‐analysis of both cohorts demonstrated that pDCs are also decreased in blood of NHOL patients and highlighted that the decrease in blood cDC type‐2 was specific for IOI patients compared to NHOL or controls. Deconvolution‐based estimation of immune cells in transcriptomic data of 48 orbital biopsies revealed a decrease in the abundance of pDC and cDC populations within the orbital microenvironment of IOI patients. Collectively, these data suggest a previously underappreciated role for dendritic cells in orbital disorders.

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Section: Discussionsupporting

confidence: 56%

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

et al. 2020

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“…These findings were largely consistent in both cohorts and are in keeping with previous studies (21–23). The cytokines IP10, sCD40L and TNFα are important mediators of B and T lymphocyte activation, inflammation and autoantibody production in SLE and the consistent elevation of these cytokines is likely a reflection of the central importance of these immune processes in SLE pathogenesis (24). Similarly, VEGF is of paramount importance in the development of vascular pathology in SLE patients and is a useful biomarker for detecting systemic involvement in these patients (5).…”

Section: Discussionmentioning

confidence: 99%

Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus

Smikle

DeCeulaer

Romay-Penabad³

et al. 2017

Lupus

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Background The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes. Methods The serum levels of several aPL, 25-hydroxy vitamin D, pro-inflammatory cytokines including IFNα, IL-1β, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican (n-=45) and Hopkins (n=267) Lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/β2glycoprotein antigenic complexes (oxLβ2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were utilized. Results Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLβ2Ag and IL-6 were elevated in the Jamaican cohort and IFNα, IL-1β and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8 and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines. Conclusions Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle complexities of vitamin D’s relationship with cytokine production and disease activity in these patients.

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“…26 In SLE patients the DC population has well-established abnormalities thus there is an increased population of plasmacytoid DC (pDC), which produce type 1 INF in response to nucleic acid via TLR7 and TLR 9 activation, a reduced conventional DC population which, in SLE, promote autoreactivity instead of self-tolerance. 27 The complement system also participates in SLE. 28 Complement consumption is one of the markers for SLE activity as inflammation leads to complement system activation and, among other functions, opsonization of IC.…”

Section: Sle Immunobiologymentioning

confidence: 99%

<p>Towards Precision Medicine in Systemic Lupus Erythematosus</p>

Lever¹,

Alves²,

Isenberg³

2020

PGPM

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Systemic lupus erythematosus (SLE) is a remarkable condition characterised by diversity amongst its clinical features and immunological abnormalities. In this review, we attempt to capture the major immunological changes linked to the pathophysiology of lupus and discuss the challenge it presents in moving towards the concept of precision medicine. Currently broadly similar types of drugs, e.g., steroids, immunosuppressives, hydroxychloroquine are used to treat many of the diverse clinical features of SLE. We suspect that, as the precise immunopathological abnormalities differ between the various organs/systems in lupus patients, it will be some time before precision medicine can be fully applied to SLE.

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Dendritic Cells in Systemic Lupus Erythematosus: From Pathogenic Players to Therapeutic Tools

Cited by 50 publications

References 143 publications

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

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

Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus

<p>Towards Precision Medicine in Systemic Lupus Erythematosus</p>

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