1 Ocak 2021 Dergi makalesi Açık Erişim

Taft, Justin; Markson, Michael; Legarda, Diana; Patel, Roosheel; Chan, Mark; Malle, Louise; Richardson, Ashley; Gruber, Conor; Martin-Fernandez, Marta; Mancini, Grazia M. S.; van Laar, Jan A. M.; van Pelt, Philomine; Buta, Sofija; Wokke, Beatrijs H. A.; Sabli, Ira K. D.; Sancho-Shimizu, Vanessa; Chavan, Pallavi Pimpale; Schnappauf, Oskar; Khubchandani, Raju; Cuceoglu, Muserref Kasap; Cuceoglu, Muserref Kasap

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{
  "@context": "https://schema.org/", 
  "@id": 230168, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "name": "Taft, Justin"
    }, 
    {
      "@type": "Person", 
      "name": "Markson, Michael"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA", 
      "name": "Legarda, Diana"
    }, 
    {
      "@type": "Person", 
      "name": "Patel, Roosheel"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Mayo Clin, Dept Immunol, Rochester, MN 55905 USA", 
      "name": "Chan, Mark"
    }, 
    {
      "@type": "Person", 
      "name": "Malle, Louise"
    }, 
    {
      "@type": "Person", 
      "name": "Richardson, Ashley"
    }, 
    {
      "@type": "Person", 
      "name": "Gruber, Conor"
    }, 
    {
      "@type": "Person", 
      "name": "Martin-Fernandez, Marta"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Erasmus MC, Dept Clin Genet, NL-3015 GD Rotterdam, Netherlands", 
      "name": "Mancini, Grazia M. S."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Erasmus MC, Dept Immunol, NL-3015 GD Rotterdam, Netherlands", 
      "name": "van Laar, Jan A. M."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Erasmus MC, Dept Rheumatol, NL-3015 GD Rotterdam, Netherlands", 
      "name": "van Pelt, Philomine"
    }, 
    {
      "@type": "Person", 
      "name": "Buta, Sofija"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Erasmus MC, Dept Neurol, NL-3015 GD Rotterdam, Netherlands", 
      "name": "Wokke, Beatrijs H. A."
    }, 
    {
      "@type": "Person", 
      "name": "Sabli, Ira K. D."
    }, 
    {
      "@type": "Person", 
      "name": "Sancho-Shimizu, Vanessa"
    }, 
    {
      "@type": "Person", 
      "name": "Chavan, Pallavi Pimpale"
    }, 
    {
      "@type": "Person", 
      "affiliation": "NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA", 
      "name": "Schnappauf, Oskar"
    }, 
    {
      "@type": "Person", 
      "name": "Khubchandani, Raju"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Hacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey", 
      "name": "Cuceoglu, Muserref Kasap"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Hacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey", 
      "name": "Cuceoglu, Muserref Kasap"
    }
  ], 
  "datePublished": "2021-01-01", 
  "description": "TANK binding kinase 1 (TBK1) regulates IFN-I, NF-kappa B, and TNF-induced RIPK1-dependent cell death (RCD). In mice, biallelic loss of TBK1 is embryonically lethal. We discovered four humans, ages 32, 26, 7, and 8 from three unrelated consanguineous families with homozygous loss-of-function mutations in TBK1. All four patients suffer from chronic and systemic autoinflammation, but not severe viral infections. We demonstrate that TBK1 loss results in hypomorphic but sufficient IFN-I induction via RIG-I/MDA5, while the system retains near intact IL-6 induction through NF-kappa B. Autoinflammation is driven by TNF-induced RCD as patient-derived fibroblasts experienced higher rates of necroptosis in vitro, and CC3 was elevated in peripheral blood ex vivo. Treatment with anti-TNF dampened the baseline circulating inflammatory profile and ameliorated the clinical condition in vivo. These findings highlight the plasticity of the IFN-I response and underscore a cardinal role for TBK1 in the regulation of RCD.", 
  "headline": "Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death", 
  "identifier": 230168, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death", 
  "url": "https://aperta.ulakbim.gov.tr/record/230168"
}