Phenotypic analysis of retinal leukocyte infiltration during combined cyclosporin a and nasal antigen administration of retinal antigens: delay and inhibition of macrophage and granulocyte infiltration

Dick, Andrew D.; Kreutzer, B; Laliotou, Barbara; Forrester, John V.

doi:10.3109/09273949709085061

Cited by 15 publications

(7 citation statements)

References 24 publications

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“…However, subsequent extensive investigations of the microglial cell have concluded that its main role is an immunosuppressive one, at least in the non‐inflamed retina (77–79). Instead, a second very small population of perivascular MHC class II + DCs and macrophages that line the retinal vessels in meningeal extensions were thought to be cells with the potential to initiate retinal inflammation (80) (). These cells are analogous to the perivascular CD11c + cells in the brain parenchyma, which, in elegant conditional knockout studies, have been shown to be required for induction of experimental autoimmune encephalitis (EAE) in mice (81).…”

Section: Myeloid Cells In Ocular Tissuesmentioning

confidence: 99%

Dendritic cell physiology and function in the eye

Forrester

Kuffová

et al. 2010

Immunological Reviews

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176

143

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The eye and the brain are immunologically privileged sites, a property previously attributed to the lack of a lymphatic circulation. However, recent tracking studies confirm that these organs have good communication through classical site-specific lymph nodes, as well as direct connection through the blood circulation with the spleen. In addition, like all tissues, they contain resident myeloid cell populations that play important roles in tissue homeostasis and the response to foreign antigens. Most of the macrophage and dendritic cell (DC) populations in the eye are restricted to the supporting connective tissues, including the cornea, while the neural tissue (the retina) contains almost no DCs, occasional macrophages (perivascularly distributed), and a specialized myeloid cell type, the microglial cell. Resident microglial cells are normally programmed for immunological tolerance. The privileged status of the eye, however, is relative, as it is susceptible to immune-mediated inflammatory disease, both infectious and autoimmune. Intraocular inflammation (uveitis and uveoretinitis) and corneal graft rejection constitute two of the more common inflammatory conditions affecting the eye leading to considerable morbidity (blindness). As corneal graft rejection occurs almost exclusively by indirect allorecognition, host DCs play a major role in this process and are likely to be modified in their behavior by the ocular microenvironment. Ocular surface disease, including allergy and atopy, also comprise a significant group of immune-mediated eye disorders in which DCs participate, while infectious disease such as herpes simplex keratitis is thought to be initiated via corneal DCs. Intriguingly, some more common conditions previously thought to be degenerative (e.g. age-related macular degeneration) may have an autoimmune component in which ocular DCs and macrophages are critically involved. Recently, the possibility of harnessing the tolerizing potential of DCs has been applied to experimental models of autoimmune uveoretinitis with good effect. This approach has considerable potential for use in translational clinical therapy to prevent sight-threatening disease caused by ocular inflammation.

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Section: Myeloid Cells In Ocular Tissuesmentioning

confidence: 99%

Dendritic cell physiology and function in the eye

Forrester

Kuffová

et al. 2010

Immunological Reviews

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176

143

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“…EAU is induced in mice by immunization with retinal antigens, and is a model for human posterior uveitis, a potentially blinding inflammatory ocular condition that affects the choroid of the eye and the neural retina (15, 16). Many studies have identified macrophages as key players in EAU, mainly in the context of the induction and effector phase of the disease (17, 18), although several reports have indicated the presence of macrophages in the resolution stage, as well (19, 20). However, in most of these studies there was no functional distinction between resident microglia and infiltrating macrophages.…”

Section: Introductionmentioning

confidence: 99%

Functional Macrophage Heterogeneity in a Mouse Model of Autoimmune Central Nervous System Pathology

London

Benhar

Mattapallil

et al. 2013

The Journal of Immunology

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Functional macrophage heterogeneity is well appreciated outside the CNS in wound healing and cancer, and was recently also demonstrated in several CNS compartments following “sterile” insults. Yet, such heterogeneity was largely overlooked in the context of inflammatory autoimmune pathology, in which macrophages were mainly associated with disease induction and propagation. Here, we show the diversity of monocyte-derived macrophages along the course of experimental autoimmune uveitis (EAU), an inflammatory condition affecting the ocular system, serving a model for CNS autoimmune pathology. Disease induction resulted in the appearance of a distinct myeloid population in the retina, and in the infiltration of monocyte-derived macrophages that were absent from control eyes. During the disease course, the frequency of CX3CR1high infiltrating macrophages that express markers associated with inflammation-resolving activity was increased, along with a decrease in the frequency of inflammation-associated, Ly6C+ macrophages. Inhibition of monocyte infiltration at the induction phase of EAU prevented disease onset, while monocyte depletion at the resolution phase resulted in a decrease in Foxp3+ regulatory T cells, and in exacerbated disease. Thus, monocyte-derived macrophages display distinct phenotypes throughout the disease course, even in an immune-induced pathology, reflecting their differential roles in disease induction and resolution.

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“…The release of inflammatory mediators leads to a leucocyte influx that consists of a complex mixture of cell types. 3,4 For example, at the peak of experimental autoimmune uveoretinitis (EAU), the murine model of human inflammatory eye disease, we observe a heterogeneous population of cells including CD11b + cells, which form the largest fraction of the immune cells present, with significant numbers of CD4 + T cells and smaller numbers of CD8 + T cells also detected. [5][6][7] In this environment, the large majority of CD11b + cells are usually described as macrophages (Mu); they release inflammatory mediators and act as professional antigen-presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

TNFR1 signalling is a critical checkpoint for developing macrophages that control of T‐cell proliferation

et al. 2010

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SummaryMacrophages (Mu) are professional antigen-presenting cells, but when they accumulate at sites of inflammation, they can inhibit T-cell proliferation. In experimental autoimmune uveoretinitis, this limits the expansion of T cells within the target organ. To define requirements for the elaboration of this outcome, we have generated populations of Mu in vitro that could also regulate T-cell responses; stimulating CD4 + T-cell activation and cytokine production, but simultaneously suppressing T-cell proliferation. When T cells are removed from the influence of such cells, normal T-cell responses are restored. We show that tumour necrosis factor 1 (TNFR1) signalling is a critical checkpoint in the development of such Mu, as TNFR1 )/) Mu are unable to suppress T-cell proliferation. This deficit in antigen-presenting cells results in a lack of production of prostaglandin E 2 (PGE 2 ) and nitric oxide, which are critical effector mechanisms that inhibit T-cell division. However, TNFR1 signalling is not required for the inhibitory function of Mu because we could circumvent the requirement for this receptor, by maturing Mu in the presence of exogenous interferon-c and PGE 2 . This produced TNFR1 )/) Mu that inhibited T-cell proliferation and indicates that TNFR1 delivers a signal that is necessary for the development but not the execution of this function.

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Phenotypic analysis of retinal leukocyte infiltration during combined cyclosporin a and nasal antigen administration of retinal antigens: delay and inhibition of macrophage and granulocyte infiltration

Abstract: Nasal antigen administration successfully suppresses a model of organ-specific autoimmune disease, experimental autoimmune uveoretinitis (EAU)

Cited by 15 publications

References 24 publications

Dendritic cell physiology and function in the eye

Dendritic cell physiology and function in the eye

Functional Macrophage Heterogeneity in a Mouse Model of Autoimmune Central Nervous System Pathology

TNFR1 signalling is a critical checkpoint for developing macrophages that control of T‐cell proliferation

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