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- Title
Synthetic cytokine receptors transmit biological signals using arti?cial ligands.
- Authors
Engelowski, Erika; Schneider, Artur; Franke, Manuel; Haifeng Xu; Clemen, Ramona; Lang, Alexander; Baran, Paul; Binsch, Christian; Knebel, Birgit; Al-Hasani, Hadi; Moll, Jens M.; Floß, Doreen M.; Lang, Philipp A.; Scheller, Jürgen
- Abstract
Cytokine-induced signal transduction is executed by natural biological switches, which among many others control immune-related processes. Here, we show that synthetic cytokine receptors (SyCyRs) can induce cytokine signaling using non-physiological ligands. High-affinity GFP- and mCherry-nanobodies were fused to transmembrane and intracellular domains of the IL-6/IL-11 and IL-23 cytokine receptors gp130 and IL-12Rβ1/IL-23R, respectively. Homo- and heterodimeric GFP:mCherry fusion proteins as synthetic cytokine-like ligands were able to induce canonical signaling in vitro and in vivo. Using SyCyR ligands, we show that IL-23 receptor homodimerization results in its activation and IL-23-like signal transduction. Moreover, trimeric receptor assembly induces trans-phosphorylation among cytokine receptors with associated Janus kinases. The SyCyR technology allows biochemical analyses of transmembrane receptor signaling in vitro and in vivo, cell-specific activation through SyCyR ligands using transgenic animals and possible therapeutic regimes involving non-physiological targets during immunotherapy.
- Subjects
SYNTHETIC receptors; CYTOKINE receptors; SYNTHETIC proteins; JANUS kinases; LIGANDS (Biochemistry); INTERLEUKIN-23
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04454-8