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

Dublin Core

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  <dc:creator>Taft, Justin</dc:creator>
  <dc:creator>Markson, Michael</dc:creator>
  <dc:creator>Legarda, Diana</dc:creator>
  <dc:creator>Patel, Roosheel</dc:creator>
  <dc:creator>Chan, Mark</dc:creator>
  <dc:creator>Malle, Louise</dc:creator>
  <dc:creator>Richardson, Ashley</dc:creator>
  <dc:creator>Gruber, Conor</dc:creator>
  <dc:creator>Martin-Fernandez, Marta</dc:creator>
  <dc:creator>Mancini, Grazia M. S.</dc:creator>
  <dc:creator>van Laar, Jan A. M.</dc:creator>
  <dc:creator>van Pelt, Philomine</dc:creator>
  <dc:creator>Buta, Sofija</dc:creator>
  <dc:creator>Wokke, Beatrijs H. A.</dc:creator>
  <dc:creator>Sabli, Ira K. D.</dc:creator>
  <dc:creator>Sancho-Shimizu, Vanessa</dc:creator>
  <dc:creator>Chavan, Pallavi Pimpale</dc:creator>
  <dc:creator>Schnappauf, Oskar</dc:creator>
  <dc:creator>Khubchandani, Raju</dc:creator>
  <dc:creator>Cuceoglu, Muserref Kasap</dc:creator>
  <dc:creator>Cuceoglu, Muserref Kasap</dc:creator>
  <dc:date>2021-01-01</dc:date>
  <dc: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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/230168</dc:identifier>
  <dc:identifier>oai:aperta.ulakbim.gov.tr:230168</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>CELL 184(17) 4447-+</dc:source>
  <dc:title>Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>