Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization |
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Authors: | Dr Tessa Lühmann Valerie Spieler Dr Vera Werner Dr Marie‐Gabrielle Ludwig Dr Juliane Fiebig Prof?Dr Thomas D Mueller Prof?Dr?Dr Lorenz Meinel |
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Affiliation: | 1. Institute for Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany;2. Novartis Pharmaceuticals AG, Basel, Switzerland;3. Lehrstuhl für Botanik I Molekulare Pflanzenphysik und Biophysik, University of Würzburg, Würzburg, Germany |
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Abstract: | Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity. |
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Keywords: | click chemistry CuAAC cytokines genetic code expansion SPAAC unnatural amino acids |
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