Aqueous Humor Suppression of Dendritic Cell Function Helps Maintain Immune Regulation in the Eye during Human Uveitis

Denniston, Alastair K; Tomlins, Paul J.; Williams, Gwyn Samuel; Kottoor, Sherine Hermangild; Khan, Imran; Oswal, K. S.; Salmon, Mike; Wallace, Graham R.; Rauz, Saaeha; Murray, Philip I.; Curnow, S. John

doi:10.1167/iovs.11-8802

Cited by 19 publications

(17 citation statements)

References 33 publications

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“…Hence, DCs not only are crucial for inducing primary immune responses, but also may be relevant for generating immunological tolerance and for the regulation of the T-cell-mediated immune response type [ 18 , 38 ]. Thus, during human uveitis, the aqueous humor suppression of DCs helps maintain immune regulation in the eye [ 39 ].…”

Section: Monocytes Macrophages and Dendritic Cells In The Eyementioning

confidence: 99%

Macrophages and Uveitis in Experimental Animal Models

Mérida

Palacios

Bosch‐Morell

2015

Mediators of Inflammation

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Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

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Section: Monocytes Macrophages and Dendritic Cells In The Eyementioning

confidence: 99%

Macrophages and Uveitis in Experimental Animal Models

Mérida

Palacios

Bosch‐Morell

2015

Mediators of Inflammation

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“…Blood DCs contain three subsets: CD1c + (BDCA1) myeloid dendritic cell 1 (mDC1), CD141 + (BDCA3) myeloid dendritic cell 2 (mDC2), and CD303 + (BDCA2) plasmacytoid DCs (pDCs) [9], which are from Lineage 1 − (Lin1, including CD3, CD14, CD16, CD19, CD20 and CD56) HLADR + cells. Myeloid DCs actively infiltrate into the eye and can be seen suspending in the aqueous humor of uveitis patients [10]. …”

Section: Introductionmentioning

confidence: 99%

Increased CD1c+ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease

Chen

Denniston

Hannes

et al. 2015

Clinical Immunology

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In this study we investigated the role of blood CD1c+ myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c+ mDC1 in uveitis patients. The increased CD1c+ mDC1 exhibited high HLADR expression and less antigen uptake. CD1c+ mDC1 were divided into two subpopulations. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD62L−CD4+ T helper cell proliferation. The mature phenotype and function of CD1c+ mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c+ mDC1.

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“…Similarly, Denniston et al used human MoDCs as a model to test the effects of non-inflammatory and inflammatory AqH supernatant, noting that exposure of MoDCs from healthy controls to uveitic AqH from patients with active inflammation induced upregulation of MHC I and II and reduced CD86. Interestingly these changes were characteristic of the mDCs that had been directly isolated from these uveitis patients, providing evidence for the potential role of the ocular microenvironment in DC regulation, maturation and function 15; 16 .…”

Section: Abnormalities Of Dendritic Cell Subsets In Non-infectiousmentioning

confidence: 83%

“…This may be particularly relevant to those forms of uveitis that have a proposed association with gram negative bacteria such as HLA-B27 associated anterior uveitis 5 . Denniston et al reported that mDCs isolated from human uveitic aqueous humor (AqH) were characterized by elevated MHC I and II, but reduced CD86 compared with matched peripheral blood mDCs 16 .…”

Section: Abnormalities Of Dendritic Cell Subsets In Non-infectiousmentioning

confidence: 99%

Role of dendritic cell subsets in immunity and their contribution to noninfectious uveitis

Chen

Denniston

Hirani

et al. 2015

Survey of Ophthalmology

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Dendritic cells (DCs) are a heterogeneous population. Murine DCs consist of conventional DCs (cDCs) and plasmacytoid DCs (pDCs). In human, the analogous populations are myeloid DCs (mDCs) and pDCs. Though distinct in phenotypes and functions, studies have shown that these DC subsets may interact or ‘crosstalk’ during immune responses. For example, cDCs may facilitate pDC maturation, while pDCs may enhance antigen presentation of cDCs in certain pathogenic conditions or even take on a cDC phenotype themselves. The role of DCs in non-infectious uveitis has been studied primarily in the experimental autoimmune uveitis mouse model and to a more limited extent in patients. Recent evidence shows that the number, phenotype and function of DC subsets are altered in this disease. We provide an overview of selected recent developments of pDCs and cDCs/mDCs, with special attention to their interaction and the dual roles of DC subsets in non-infectious uveitis.

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Aqueous Humor Suppression of Dendritic Cell Function Helps Maintain Immune Regulation in the Eye during Human Uveitis

Abstract: These data indicate that the ocular microenvironment continues to regulate DC function during uveitis, despite IFNγ-driven upregulation of MHC expression, supporting the hypothesis that immune regulation within the eye is maintained during inflammation.

Cited by 19 publications

References 33 publications

Macrophages and Uveitis in Experimental Animal Models

Macrophages and Uveitis in Experimental Animal Models

Increased CD1c+ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease

Role of dendritic cell subsets in immunity and their contribution to noninfectious uveitis

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