Interleukin-4-Clicked Surfaces Drive M2 Macrophage Polarization.
Driving macrophage (Mϕ) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin-4 (IL-4) promotes polarization into the M2-Mϕ 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 Mϕ. The approach provides a blueprint for the engineering of cytokine-activated surfaces profiled for sustained and spatially controlled activity.
Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Tessa
T
Lühmann
Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Valerie
V
Spieler
Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Vera
V
Werner
Novartis Pharmaceuticals AG, Lichtstrasse 35, 4056, Basel, Switzerland.
Marie-Gabrielle
MG
Ludwig
Lehrstuhl für Botanik I Molekulare Pflanzenphysik und Biophysik, University of Würzburg, Julius-von-Sachs-Platz 2, 97082, Würzburg, Germany.
Juliane
J
Fiebig
Lehrstuhl für Botanik I Molekulare Pflanzenphysik und Biophysik, University of Würzburg, Julius-von-Sachs-Platz 2, 97082, Würzburg, Germany.
Thomas D
TD
Mueller
Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Lorenz
L
Meinel
D000480:Alkynes / Q000737:chemistry; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D005815:Genetic Code; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D016297:Mutagenesis, Site-Directed; D012685:Sepharose / Q000737:chemistry; D013499:Surface Properties
D000480:Alkynes; D000596:Amino Acids; D001386:Azides; D008070:Lipopolysaccharides; D015847:Interleukin-4; D003300:Copper; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D012685:Sepharose; C456839:pyrrolysine; D008239:Lysine
CuAAC; SPAAC; click chemistry; cytokines; genetic code expansion; unnatural amino acids