Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization. (19th October 2016)

• Record Type: Journal Article
• Authors: Lühmann, Tessa; Spieler, Valerie; Werner, Vera; Ludwig, Marie‐Gabrielle; Fiebig, Juliane; Mueller, Thomas D.; Meinel, Lorenz
• Is Part Of: Chembiochem. Volume 17:Number 22(2016)
• Page Start: 2123
• Page End: 2128
• Publication Date: 2016-10-19
• Subjects: click chemistry -- CuAAC -- cytokines -- genetic code expansion -- SPAAC -- unnatural amino acids; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600480
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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. Abstract : Tissue repair is supported by M2‐polarized macrophages. Interleukin‐4 (IL‐4) muteins were generated by introducing unnatural amino acids into the immune‐modulating cytokine for CuAAC‐ and SPAAC‐based site‐directed surface decoration. The approach provides a blueprint for the engineering of cytokine‐activated surfaces with sustained activity.