Type I interferon pathway in adult and juvenile dermatomyositis

Baechler, Emily C.; Bilgiç, Hatice; Reed, Ann M.

doi:10.1186/ar3531

Cited by 120 publications

(104 citation statements)

References 42 publications

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“…This type 1 IFN profile was found to reflect disease activity in both DM and PM patients, highlighting its potential as a possible biomarker [72,[84][85][86][87]. The serum levels of IFN-α were found to be significantly higher in DM, PM and IMNM patients compared to IBM.…”

Section: Blood/serummentioning

confidence: 84%

“…Such gene array studies have identified a prominent type I IFN genetic signature in DM muscle in comparison with other forms of myositis [72,78]. However, expression of IFN-α and IFN-β and their inducible genes is not exclusively specific to DM and also occurs in PM [1,78], and PM patients have shown responsiveness to anti-IFN-α therapy [73,79].…”

Section: Muscle Tissuementioning

confidence: 99%

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Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Moran

Mastaglia

2014

Clinical and Experimental Immunology

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SummaryThe idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by diffuse muscle weakness and inflammation. A common immunopathogenic mechanism is the cytokine-driven infiltration of immune cells into the muscle tissue. Recent studies have further dissected the inflammatory cell types and associated cytokines involved in the immune-mediated myopathies and other chronic inflammatory and autoimmune disorders. In this review we outline the current knowledge of cytokine expression profiles and cellular sources in the major forms of inflammatory myopathy and detail the known mechanistic functions of these cytokines in the context of inflammatory myositis. Furthermore, we discuss how the application of this knowledge may lead to new therapeutic strategies for the treatment of the inflammatory myopathies, in particular for cases resistant to conventional forms of therapy.

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Section: Blood/serummentioning

confidence: 84%

Section: Muscle Tissuementioning

confidence: 99%

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Moran

Mastaglia

2014

Clinical and Experimental Immunology

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“…Total RNA was isolated using the RNeasy minikit (Qiagen) per the manufacturer's instructions. 1 g of total cellular mRNA was reverse transcribed into cDNA using the Omniscript RT kit (Qiagen) and oligo(dT) [12][13][14][15][16][17][18] primers (Life Technologies). Realtime PCR was carried out using an ABI7500 sequence detection system (Applied Biosystems) using commercially available FAM-labeled probes and primers (Applied Biosystems) to determine mRNA expression of Ip10, Dapk1, Slfn2, and Gapdh.…”

Section: ϫ/ϫmentioning

confidence: 99%

“…Interferons (IFNs) are pleiotropic cytokines that possess antiviral, immunomodulatory, growth-inhibitory, and cytotoxic properties (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). IFNs were among the earliest biologic therapeutic agents used to treat viral infections, certain solid tumors, hematologic cancers, and some autoimmune disorders (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

“…IFNs were among the earliest biologic therapeutic agents used to treat viral infections, certain solid tumors, hematologic cancers, and some autoimmune disorders (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). IFN␥, the only type II IFN, signals through a multimeric receptor complex, IFNGR, consisting of two different chains: the IFN␥ receptor binding subunit (IFNGR1) and a transmembrane accessory factor (IFNGR2) (14,15).…”

mentioning

confidence: 99%

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Central Regulatory Role for SIN1 in Interferon γ (IFNγ) Signaling and Generation of Biological Responses

Kroczyńska

Blyth

Rafidi

et al. 2017

Journal of Biological Chemistry

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Edited by Charles E. SamuelThe precise signaling mechanisms by which type II IFN receptors control expression of unique genes to induce biological responses remain to be established. We provide evidence that Sin1, a known element of the mammalian target of rapamycin complex 2 (mTORC2), is required for IFN␥-induced phosphorylation and activation of AKT and that such activation mediates downstream regulation of mTORC1 and its effectors. These events play important roles in the assembly of the eukaryotic translation initiation factor 4F (eIF4F) and mRNA translation of IFN-stimulated genes. Interestingly, IFN␥-induced tyrosine phosphorylation of STAT1 is reduced in cells with targeted disruption of Sin1, leading to decreased transcription of several IFN␥-inducible genes in an mTORC2-independent manner. Additionally, our studies establish that Sin1 is essential for generation of type II IFN-dependent antiviral effects and antiproliferative responses in normal and malignant hematopoiesis. Together, our findings establish an important role for Sin1 in both transcription and translation of IFN-stimulated genes and type II IFN-mediated biological responses, involving both mTORC2-dependent and -independent functions.Interferons (IFNs) are pleiotropic cytokines that possess antiviral, immunomodulatory, growth-inhibitory, and cytotoxic properties (1-13). IFNs were among the earliest biologic therapeutic agents used to treat viral infections, certain solid tumors, hematologic cancers, and some autoimmune disorders (1-13). IFN␥, the only type II IFN, signals through a multimeric receptor complex, IFNGR, consisting of two different chains: the IFN␥ receptor binding subunit (IFNGR1) and a transmembrane accessory factor (IFNGR2) (14,15). Engagement of IFN␥ with IFNGR leads to activation of the Janus kinases, JAK1 and JAK2, leading to tyrosine phosphorylation and activation of STAT1 (14 -18). Upon activation, STAT1 homodimers bind DNA at IFN␥-activated site elements, leading to transcription of IFN-stimulated genes (ISGs) 6 (15-18). There is evidence for different signaling pathways that are activated by IFNGR. These include protein kinase C (PKC), MAPK, Mnk kinase, PI3K/AKT, and mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 signaling cascades (19 -29). mTOR pathways promote mRNA translation in an mTOR/4E-BP1-dependent manner (25,(27)(28)(29)(30)(31)(32)(33). In previous studies, our group showed that AKT/mTOR pathways are engaged in IFN␥ signaling and control initiation of mRNA translation of ISGs (25,27,28,30). The 289-kDa mTOR kinase contains binding sites for multiple proteins regulating its activity or mediating its signals and consists of at least two independent multiprotein complexes: mTORC1 and mTORC2 (34 -38). mTORC1 is formed by mTOR, mLST8/G␤L (mammalian lethal with Sec13 protein 8/G-protein ␤-protein subunit-like), Raptor (rapamycin-sensitive companion of mTOR), Pras40 (Akt/PKB substrate 40 kDa), and Deptor (DEP domain-containing mTOR-interacting protein) and is sensitive to allosteric inhibitors, such ...

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Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus and Juvenile Dermatomyositis

Moraitis

Eleftheriou

2019

Harper's Textbook of Pediatric Dermatology

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Type I interferon pathway in adult and juvenile dermatomyositis

Cited by 120 publications

References 42 publications

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Central Regulatory Role for SIN1 in Interferon γ (IFNγ) Signaling and Generation of Biological Responses

Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus and Juvenile Dermatomyositis

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