Constitutive and Cytokine-Induced GITR Ligand Expression on Human Retinal Pigment Epithelium and Photoreceptors

Kim, Ben J.; Li, Zhuqing; Fariss, Robert N.; Shen, De Fen; Mahesh, Sankaranarayana P.; Egwuagu, Charles E.; Yu, Cheng‐Rong; Nagineni, Chandrasekharam N.; Chan, Chi‐Chao; Nussenblatt, Robert B.

doi:10.1167/iovs.03-0919

Cited by 29 publications

(25 citation statements)

References 28 publications

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“…GITR, which is preferentially expressed on the surface of Treg, potentially provides a signal that abrogates Treg suppression (9). GITRL is constitutively expressed on retinal pigment epithelium and photoreceptor inner segments in high levels and participates in the regulation of ocular inflammation (13). GITRL may be the crucial factor for tumorigenesis and the aggressive biological behavior of human peripheral primitive neuroectodermal tumor (21).…”

Section: Discussionmentioning

confidence: 99%

“…Engagement of GITR on effector T cells by its ligand mediates resistance to suppression by CD4 + CD25 + T cells (12). GITRL is constitutively expressed on cultured retinal pigment epithelium and in high levels on photoreceptor inner segments (13). But little is known about the expression profiles of GITR in human peripheral T cells either in healthy individuals or in the patients with autoimmune diseases and cancer.…”

Section: Introductionmentioning

confidence: 99%

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Expression of AITR and AITR ligand in breast cancer patients

Kim

Jung²,

Choi³

et al. 2007

Oncol Rep

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Abstract. Human activation-inducible TNF receptor (AITR) is a new member of the tumor necrosis factor family and expressed on peripheral blood mononuclear cells (PBMC) and leukocytes. Its ligand (AITRL) is expressed in endothelial cells. This study aimed to evaluate the presence and role of AITR and AITRL in patients with breast cancer. Expression of AITR and AITRL on PBMC and breast cancer cells was determined by flow cytometry, RT-PCR and fluorescence microscopy. Soluble (s) AITR and sAITRL were detected in serum of breast cancer patients by ELISA. AITR and AITRL were constitutively expressed in T cells, B cells, monocytes and monocyte-derived dendritic cells of breast cancer patients. AITRL was overexpressed in breast cancer cells. The levels of sAITRL were significantly increased in serum of breast cancer patients compared with the healthy control. This study suggests that AITR and AITRL may play an important role in tumor growth and survival in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of AITR and AITR ligand in breast cancer patients

Kim

Jung²,

Choi³

et al. 2007

Oncol Rep

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“…41,42 The glucocorticoid-induced TNF related receptor ligand (GITRL) is a receptor that has been associated with the abrogation of immunoregulation associated with the CD25 subpopulation of CD4 T cells. 43 It has been further shown to be constitutively expressed at low levels in the human eye, including the RPE. 43 Enhancing GITRL expression on human RPE cells has been shown to have a marked effect on the immune response.…”

Section: The Retinal Pigment Epithelium and The Immune Responsementioning

confidence: 99%

“…43 It has been further shown to be constitutively expressed at low levels in the human eye, including the RPE. 43 Enhancing GITRL expression on human RPE cells has been shown to have a marked effect on the immune response. A downregulation of CD3+ T cells is usually noted when RPE cells are co-cultured with these cells, and this downregulation is associated with a large production of TGF-beta.…”

Section: The Retinal Pigment Epithelium and The Immune Responsementioning

confidence: 99%

Age-related Macular Degeneration and the Immune Response: Implications for Therapy

Nussenblatt

Ferris

2007

American Journal of Ophthalmology

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115

101

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Purpose-Review of the available information concerning the immune mediation of age related macular degeneration (AMD); speculate on proposed mechanisms and immuno-therapy. Design-Interpretative essay Methods-Literature review and interpretationResults-An ever growing body of evidence is gathering concerning the role of the immune system in AMD. Evidence to date suggests that the underlying mechanism leading to AMD is the decline of the ocular downregulatory immune environment (DIE). The subsequent activation of the immune system would lead to T cell sensitization. When combined with local anti-angiogenic therapy, several existing immuno-therapies could be used to downregulate the immune response and potentially leading to a more efficient inhibition of choroidal neovascularization.Age related macular degeneration is currently the leading cause of blindness in the United States and its prevalence will continue to increase in the coming decades unless new prevention strategies can be developed. 1 Currently over 1.75 million US citizens are affected with advanced AMD, and this number is likely to increase to nearly 3 million by the year 2020 due to the increased number of aging US citizens. Population studies have helped to determine risk factors for this disorder. 2 Some of the non-modifiable factors include age, family history/ genetic factors, light colored iris, and hyperopia. Some of the modifiable risk factors include cigarette smoking, diet, high blood pressure, and possibly elevated serum cholesterol or increased light exposure. The association of these risk factors with the risk of advanced AMD can provide clues as to what causes the disease to develop and how one might prevent the disease. For example, cigarette smoking may increase the risk of AMD through enhancement of the immune cascade. 3 The progression of AMD may be similar to the mechanisms of progression for atherosclerosis, which is now considered to be an inflammatory disease. 4 This provides a new approach to understanding the development and potentially the treatment of this disease. The atheromatous lesion is believed to be inflammatory and it is conjectured that the autoantigen LDL is a driving factor. 5,6 The immune response and cytokine status appear to have profound effects on the disease, with IL-10 loss associated with an increase in the numbers of atheromatous lesions, while deficiencies in IFN-gamma and IL-18 are associated

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“…In addition, GITR expression has been detected on human NK cells and macrophages [4,5]. GITR is mainly triggered by the ligand GITRL (TNFSF18, a type II transmembrane protein of the TNF superfamily), which has been found in dendritic cells (DCs), endothelial cells, macrophages and retinal pigment epithelium and photoreceptors in humans [6][7][8], and is also activated by a newly described ligand named SECTM1A in mice [9]. A soluble form of GITRL could be detected in the sera of patients with primary Sjögren's syndrome [10], systemic lupus erythematosus [11], Hashimoto's thyroiditis [12], or malignancy [13,14].…”

Section: Introductionmentioning

confidence: 99%

GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis

Wen

Jia

et al. 2016

Clin Rheumatol

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The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA.

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Constitutive and Cytokine-Induced GITR Ligand Expression on Human Retinal Pigment Epithelium and Photoreceptors

Cited by 29 publications

References 28 publications

Expression of AITR and AITR ligand in breast cancer patients

Expression of AITR and AITR ligand in breast cancer patients

Age-related Macular Degeneration and the Immune Response: Implications for Therapy

GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis

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