IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice

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2021
Autor:innen
Koss, Carolin K.
Baker, Jonathan R.
Tilp, Cornelia
Przibilla, Michèl
Lerner, Carmen
Frey, Silvia
Keck, Martina
El Kasmi, Karim C.
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Communications biology. Springer Nature. 2021, 4, 172. eISSN 2399-3642. Available under: doi: 10.1038/s42003-021-01703-3
Zusammenfassung

IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.

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570 Biowissenschaften, Biologie
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ISO 690KOSS, Carolin K., Christian T. WOHNHAAS, Jonathan R. BAKER, Cornelia TILP, Michèl PRZIBILLA, Carmen LERNER, Silvia FREY, Martina KECK, Florian GANTNER, Karim C. EL KASMI, 2021. IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice. In: Communications biology. Springer Nature. 2021, 4, 172. eISSN 2399-3642. Available under: doi: 10.1038/s42003-021-01703-3
BibTex
@article{Koss2021-02-08criti-53146,
  year={2021},
  doi={10.1038/s42003-021-01703-3},
  title={IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice},
  volume={4},
  journal={Communications biology},
  author={Koss, Carolin K. and Wohnhaas, Christian T. and Baker, Jonathan R. and Tilp, Cornelia and Przibilla, Michèl and Lerner, Carmen and Frey, Silvia and Keck, Martina and Gantner, Florian and El Kasmi, Karim C.},
  note={Article Number: 172}
}
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