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Bank, Ute; Deiser, Katrin; Plaza-Sirvent, Carlos; Osbelt, Lisa; Witte, Amelie; Knop, Laura; Labrenz, Rebecca; Jänsch, Robert; Richter, Felix; Biswas, Aindrila; Zenclussen, Ana C.; Vivier, Eric; Romagnani, Chiara; Kühl, Anja A.; Dunay, Ildiko R.; Strowig, Till; Schmitz, Ingo; Schüler, Thomas

c-FLIP is crucial for IL-7/IL-15-dependent NKp46+ ILC development and protection from intestinal inflammation in mice

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  • Medientyp: E-Artikel
  • Titel: c-FLIP is crucial for IL-7/IL-15-dependent NKp46+ ILC development and protection from intestinal inflammation in mice
  • Beteiligte: Bank, Ute; Deiser, Katrin; Plaza-Sirvent, Carlos; Osbelt, Lisa; Witte, Amelie; Knop, Laura; Labrenz, Rebecca; Jänsch, Robert; Richter, Felix; Biswas, Aindrila; Zenclussen, Ana C.; Vivier, Eric; Romagnani, Chiara; Kühl, Anja A.; Dunay, Ildiko R.; Strowig, Till; Schmitz, Ingo; Schüler, Thomas
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-020-14782-3
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>NKp46<jats:sup>+</jats:sup> innate lymphoid cells (ILC) modulate tissue homeostasis and anti-microbial immune responses. ILC development and function are regulated by cytokines such as Interleukin (IL)−7 and IL-15. However, the ILC-intrinsic pathways translating cytokine signals into developmental programs are largely unknown. Here we show that the anti-apoptotic molecule cellular FLICE-like inhibitory protein (c-FLIP) is crucial for the generation of IL-7/IL-15-dependent NKp46<jats:sup>+</jats:sup> ILC1, including conventional natural killer (cNK) cells, and ILC3. Cytokine-induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) precedes up-regulation of c-FLIP, which protects developing NKp46<jats:sup>+</jats:sup> ILC from TNF-induced apoptosis. NKp46<jats:sup>+</jats:sup> ILC-specific inactivation of c-FLIP leads to the loss of all IL-7/IL-15-dependent NKp46<jats:sup>+</jats:sup> ILC, thereby inducing early-onset chronic colitis and subsequently microbial dysbiosis; meanwhile, the depletion of cNK, but not NKp46<jats:sup>+</jats:sup> ILC1/3, aggravates experimental colitis. In summary, our data demonstrate a non-redundant function of c-FLIP for the generation of NKp46<jats:sup>+</jats:sup> ILC, which protect T/B lymphocyte-sufficient mice from intestinal inflammation.</jats:p>
  • Zugangsstatus: Freier Zugang