Molecular signature of neutrophil extracellular trap mediating disease module in idiopathic inflammatory myopathy
Copyright © 2023 Elsevier Ltd. All rights reserved..
The rarity and heterogeneity of idiopathic inflammatory myopathy (IIM) pose challenges for researching IIM in affected individuals. We analyzed integrated transcriptomic datasets obtained using muscle tissues from patients with five distinct IIM subtypes to investigate the shared and distinctive cellular and molecular characteristics. A transcriptomic dataset of muscle tissues from normal controls (n = 105) and patients with dermatomyositis (n = 89), polymyositis (n = 33), inclusion body myositis (n = 121), immune-mediated necrotizing myositis (n = 75), and anti-synthetase syndrome (n = 18) was used for differential gene-expression analysis, functional-enrichment analysis, gene set-enrichment analysis, disease-module identification, and kernel-based diffusion scoring. Damage-associated molecular pattern-associated pathways and neutrophil-mediated immunity were significantly enriched across different IIM subtypes, although their activities varied. Interferons-signaling pathways were differentially activated across all five IIM subtypes. In particular, neutrophil extracellular trap (NET) formation was significantly activated and correlated with Fcγ R-mediated signaling pathways. NET formation-associated genes were key for establishing disease modules, and FCGRs, C1QA, and SERPINE1 markedly perturbed the disease modules. Integrated transcriptomic analysis of muscle tissues identified NETs as key components of neutrophil-mediated immunity involved in the pathogenesis of IIM subtypes and, thus, has therapeutically targetable value.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
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| Enthalten in: |
Journal of autoimmunity - 138(2023) vom: 01. Juli, Seite 103063 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moon, Su-Jin [VerfasserIn] |
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| Links: |
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| Themen: |
Idiopathic inflammatory myopathy |
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| Anmerkungen: |
Date Completed 15.06.2023 Date Revised 15.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaut.2023.103063 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357231287 |
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| 520 | |a The rarity and heterogeneity of idiopathic inflammatory myopathy (IIM) pose challenges for researching IIM in affected individuals. We analyzed integrated transcriptomic datasets obtained using muscle tissues from patients with five distinct IIM subtypes to investigate the shared and distinctive cellular and molecular characteristics. A transcriptomic dataset of muscle tissues from normal controls (n = 105) and patients with dermatomyositis (n = 89), polymyositis (n = 33), inclusion body myositis (n = 121), immune-mediated necrotizing myositis (n = 75), and anti-synthetase syndrome (n = 18) was used for differential gene-expression analysis, functional-enrichment analysis, gene set-enrichment analysis, disease-module identification, and kernel-based diffusion scoring. Damage-associated molecular pattern-associated pathways and neutrophil-mediated immunity were significantly enriched across different IIM subtypes, although their activities varied. Interferons-signaling pathways were differentially activated across all five IIM subtypes. In particular, neutrophil extracellular trap (NET) formation was significantly activated and correlated with Fcγ R-mediated signaling pathways. NET formation-associated genes were key for establishing disease modules, and FCGRs, C1QA, and SERPINE1 markedly perturbed the disease modules. Integrated transcriptomic analysis of muscle tissues identified NETs as key components of neutrophil-mediated immunity involved in the pathogenesis of IIM subtypes and, thus, has therapeutically targetable value | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Idiopathic inflammatory myopathy | |
| 650 | 4 | |a Molecular signature | |
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| 700 | 1 | |a Park, Kyung-Su |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Ki-Jo |e verfasserin |4 aut | |
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