Activation of the JAK/STAT pathway in Behcet’s disease

Tulunay, Aysın; Dozmorov, Mikhail G.; Türe-Özdemir, Filiz; Yılmaz, Vuslat; Ekşioğlu-Demiralp, Emel; Alıbaz-Öner, Fatma; Özen, Gülşen; Wren, Jonathan D.; Saruhan‐Direskeneli, Güher; Sawalha, Amr H.; Direşkeneli, Haner

doi:10.1038/gene.2014.64

Cited by 64 publications

(60 citation statements)

References 35 publications

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“…BD also presents with heterogeneous clinical manifestations and can affect the cardiovascular, gastrointestinal, musculoskeletal, and central nervous systems [68]. The pathogenesis of BD is unclear; however, several lines of evidence indicate disease inflammation is associated with the activities of T cells and monocytes [69], the most prominent infiltrating cell types in the inflamed tissues of patients [52,70]. Furthermore, disease activity correlates with a proinflammatory shift in peripheral T cell populations featuring the expansion of both Th17 and Th22 subsets and a reduction in Tregs [71][72][73].…”

Section: Behçet's Diseasementioning

confidence: 99%

Epigenetics and Vasculitis: a Comprehensive Review

Renauer

Coit

Sawalha

2015

Clinic Rev Allerg Immunol

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Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

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Section: Behçet's Diseasementioning

confidence: 99%

Epigenetics and Vasculitis: a Comprehensive Review

Renauer

Coit

Sawalha

2015

Clinic Rev Allerg Immunol

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“…In a recent study of patients with non-refractory Hodgkin's lymphoma being treated using a PD-1 blockade immunotherapy paradigm, phosphorylated STAT3 was detected in the nucleus of Reed-Sternberg cells (the presence of which is necessary for the diagnosis of Hodgkin's lymphoma) (114). In Behcet's disease, an inflammatory disorder resulting in vasculitis, STAT3 is activated (115). In contrast, there appears to be attenuated IFN-α-induced STAT3 signaling in DCs from patients with Crohn's disease and IL-10 induces enhanced STAT3 activation, which could impact the DC's ability to present Ag (116).…”

Section: Introduction Of Cell Signaling Pathwaysmentioning

confidence: 99%

Cell Signaling Pathways That Regulate Antigen Presentation

Brutkiewicz

2016

The Journal of Immunology

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Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation--a necessary first step in the activation of innate and adaptive T cells. In this brief review, I will discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s) if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity and cancer.

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“…Tulunay et al demonstrated that the JAK1/STAT3 signaling pathway is activated in BD, and several other studies have shown similar findings [126]. Tulunay further suggested that more direct therapies aimed at JAK/STAT-associated cytokines such as ustekinumab (anti-IL12/23) and recently the approved tofacitinib that specifically inhibits JAK1/3, may be new therapeutic options for BD [126].…”

Section: Helper and Regulatory T Lymphocytes Involvement In Bdmentioning

confidence: 86%

Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease

Adeeb¹,

Khan²,

Stack³

et al. 2017

Behcet's Disease

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Behçet's disease (BD) is a type of vasculitis with many distinctive clinical manifestations and multifactorial immunopathogenesis. The cause of BD remains unknown, but it has been postulated that in a genetically predisposed or susceptible population, exogenous agents trigger the dysregulation of both autoinflammatory and autoimmune responses resulting in multisystem vasculitis. There are robust ongoing efforts across the globe to elucidate and identify signature markers to improve and assist in rapid diagnosis of the disease and to tailor the best therapy accordingly. While association of human leukocyte antigen (HLA)-B * 51 (B * 51:01 subtype) allele is well recognized as the strongest genetic susceptibility gene so far among genetically predisposed BD patients, further investigations using the latest technology have led to the identification of several novel single nucleotide polymorphisms (SNPs) and other associated genes involved in the pathogenesis. There are several "established" cytokines known to be involved in the pathogenesis of BD, which have been further implicated in the genome-wide association studies (GWAS)-based cytokine/receptor gene loci studies, as well as numerous "novel" cytokines, which are currently being studied and identified. This chapter offers insights into current knowledge and thoughts regarding the future of biomarkers in BD.

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Activation of the JAK/STAT pathway in Behcet’s disease

Cited by 64 publications

References 35 publications

Epigenetics and Vasculitis: a Comprehensive Review

Epigenetics and Vasculitis: a Comprehensive Review

Cell Signaling Pathways That Regulate Antigen Presentation

Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease

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