Cytokines as villains and potential therapeutic targets in thyroid-associated ophthalmopathy: from bench to bedside

Rajaii, Fatemeh; McCoy, Allison N.; Smith, Terry J.

doi:10.1586/17469899.2014.917960

Cited by 25 publications

(19 citation statements)

References 85 publications

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“…These autoimmune diseases are regulated by the IL-23/IL-17A axis. IL-23, secreted by dendritic cells and macrophages, maintains the phenotype and function of Th17 cells [38]. Retinoic acid receptor-related orphan receptor-γt and signal transducer and activator of transcription 3 are key regulators of the transcription of il17a and the differentiation of Th17 cells.…”

Section: Cd4+ T Cellsmentioning

confidence: 99%

The involvement of T cell pathogenesis in thyroid-associated ophthalmopathy

Huang

Fang

et al. 2018

Eye

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Thyroid-associated ophthalmoapthy (TAO) is the most common orbital disease. As an autoimmune disorder, it is caused by self-reactive lymphocytes that escape immune tolerance, but the mechanism is not fully understood. The basic process of TAO is the infiltration of immune cells in orbital tissues, the activation of orbital fibroblasts (OFs), and the proliferation and differentiation of OFs and lymphocytes. Activated OFs secrete inflammatory regulators, growth factors, and chemokines, thereby maintaining and amplifying the immune responses. The interactions between OFs and lymphocytes lead to the expansion and the remodeling of the orbital tissues, presenting the clinical manifestations of TAO. This review will focus on the role of T cell subsets (Type 1, Type 2, Type 17 helper T cells, and regulatory T cells) in the pathogenesis of TAO. However, we still need further studies to unravel the pathogenesis, to confirm current hypotheses, and to provide novel ideas for appropriate clinical treatment of TAO.

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Section: Cd4+ T Cellsmentioning

confidence: 99%

The involvement of T cell pathogenesis in thyroid-associated ophthalmopathy

Huang

Fang

et al. 2018

Eye

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“…Remarkably, contrary to the need for development of antigen-specific therapy for GO, an ever-growing number of non-specific immune-related and signal transduction molecules are being proposed as potential targets for therapy in GO. Indeed, one laboratory in the past 4 years has published data on the following molecules described to be of interest in this regard; IL-1R antagonist, IL-6, IL-8, IL-12, IL-23/IL-17, TNF alpha, Slit2, CXCL-12/CXCR4, Pen-traxin-3, PTEN, AIRE, PCP-1, and p53 [101][102][103][104][105][106][107][108]. The modified Bill Clinton campaign slogan mentioned above deserves repeating.…”

Section: F) Extrathyroidal Manifestations Of Graves' Diseasementioning

confidence: 99%

Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future

Rapoport

McLachlan

2018

Horm Metab Res

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After investigating thyroid autoimmunity for more than 40 years, we present a personal perspective on the field. Despite effective therapies for Graves’ hyperthyroidism and Hashimoto’s thyroiditis, cures are elusive. Novel forms of therapy are being developed, such as small molecule inhibitors of the TSH receptor (TSHR), but cure will require immunotherapy. This goal requires advances in understanding the pathogenesis of thyroid autoimmunity, the ‘keys’ for which are the thyroid antigens themselves. Presently, however, greater investigative focus is on non-thyroid specific immune cell types and molecules. Thyroid autoantigens are the drivers of the autoimmune response, a prime example being the TSHR. In our view, the TSHR is the culprit as well as the victim in Graves’ disease because of its unique structure. Unlike the closely related gonadotropin receptors, the TSHR cleaves into subunits and there is strong evidence that its shed extracellular A-subunit, not the holoreceptor, is the major antigen driving pathogenic thyroid stimulating autoantibodies (TSAb) development. There is no Graves’ disease of the gonads. Studies of potential antigen-specific immunotherapies require an animal model. Such models have been developed in which TSAb can be induced or, more importantly, arise spontaneously. Not appreciated until recently by thyroid investigators is that B cell surface autoantibodies are highly efficient ‘antigen receptors’ and the epitope to which an autoantibody binds influences antigen processing and which peptide is presented to T cells. These animal models and recombinant human autoantibodies cloned from Graves’ and Hashimoto’s B cells (plasma cells) are available for study by future generations.

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“…Among them, 105 were duplicated records. From the remaining 280 articles, we found 27 to be relevant according to our study criteria 1 21 22 23 24 25 26 27 28 29 31 32 33 34 35 38 39 40 41 42 43 44 45 46 47 48 49 . We further manually screened the reference lists and identified another 3 relevant studies 30 36 37 .…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, 30 articles were studied. We excluded 5 reviews 1 44 47 48 49 , 3 studies in which there were no sufficient genotypic or allelic data after communication with the authors 38 45 46 , and 1 study with duplicated samples 43 . Also excluded were 5 other studies, in which the SNPs were reported only once in the literature and not eligible for meta-analysis 27 33 35 39 40 .…”

Section: Resultsmentioning

confidence: 99%

Genetic Associations of Interleukin-related Genes with Graves’ Ophthalmopathy: a Systematic Review and Meta-analysis

Wong

Rong

Chong

et al. 2015

Sci Rep

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Graves’ ophthalmopathy (GO) is the commonest extra-thyroidal manifestation of Graves’ disease (GD). Associations between interleukin-related (IL) gene polymorphisms and GO have been reported in different populations. We aim to confirm such associations by conducting a meta-analysis. Totally 382 publications were retrieved in MEDLINE and EMBASE up to 25/2/2015. After removing the duplicates and assessing the studies, we retrieved 16 studies that met the selection criteria for meta-analysis, involving 12 polymorphisms in 8 IL-related genes, and 1650 GO cases and 2909 GD controls. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated. We found one polymorphism in IL1A (rs1800587, c.-889C>T) showing a suggestive association with GO in the meta-analysis (allelic model [T vs. C]: OR = 1.62, 95% CI: 1.00–2.62, P = 0.050, I2 = 53.7%; recessive model [TT vs. TC + CC]: OR = 2.39, 95% CI: 1.07–5.37, P = 0.039, I2 = 23.6%; heterozygous model [TC vs. CC]: OR = 1.52, 95% CI: 1.04–2.22, P = 0.034, I2 = 37.0%). No association with GO was detected for the other 7 genes (IL1B, IL1RA, IL4, IL6, IL12B, IL13 and IL23R). Our results thus indicate that IL1A is likely to be a genetic biomarker for GO. Further studies with larger sample sizes are warranted to confirm the associations of IL1A and other IL-related genes with GO.

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Cytokines as villains and potential therapeutic targets in thyroid-associated ophthalmopathy: from bench to bedside

Cited by 25 publications

References 85 publications

The involvement of T cell pathogenesis in thyroid-associated ophthalmopathy

The involvement of T cell pathogenesis in thyroid-associated ophthalmopathy

Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future

Genetic Associations of Interleukin-related Genes with Graves’ Ophthalmopathy: a Systematic Review and Meta-analysis

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