Synthetic cytokine receptors transmit biological signals using artificial ligands

Erika Engelowski, Artur Schneider, Manuel Franke, Haifeng Xu, Ramona Clemen, Alexander Lang, Paul Baran, Christian Binsch, Birgit Knebel, Hadi Al-Hasani, Jens M. Moll, Doreen M. Floß, Philipp A. Lang and Jürgen Scheller ()
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Erika Engelowski: Heinrich-Heine-University
Artur Schneider: Heinrich-Heine-University
Manuel Franke: Heinrich-Heine-University
Haifeng Xu: Heinrich-Heine-University
Ramona Clemen: Heinrich-Heine-University
Alexander Lang: Heinrich-Heine-University
Paul Baran: Heinrich-Heine-University
Christian Binsch: Heinrich-Heine-University
Birgit Knebel: Heinrich-Heine-University
Hadi Al-Hasani: Heinrich-Heine-University
Jens M. Moll: Heinrich-Heine-University
Doreen M. Floß: Heinrich-Heine-University
Philipp A. Lang: Heinrich-Heine-University
Jürgen Scheller: Heinrich-Heine-University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04454-8

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DOI: 10.1038/s41467-018-04454-8

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