Dual-functionalized graphene oxide induces M2a and M2c macrophage polarization to orchestrate inflammation and tissue remodeling
Hui Li, Hefeng Yang, Bo Ma, Jia Qiao, Fanfan Chen, P. S. Wang, Riyue Yu, Jingjing Sun, Yuanwei Chen
Abstract
M2c phenotype polarization. The efficient delivery of IL4 or IL10 plasmid DNA using GPPF (GPPF/pIL4 or GPPF/pIL10) significantly enhanced macrophage cellular elongation and reduced MHC-II-associated antigen presentation. M2a(GPPF/pIL4) and M2c(GPPF/pIL10) were validated as negative regulators of the immune response and positive regulators of Th2 effectors. Up-regulated genes in M2a(GPPF/pIL4) even inhibited type I interferon production and restricted the innate immune response. Supplemental to the established data, M2a(GPPF/pIL4) behaved similar to IFN-responsive macrophages, restricting viral life cycles and promoting myogenesis and osteogenesis. Meanwhile, M2c(GPPF/pIL10) was characterized using IL10 signaling, anti-fibrosis, and neutrophil-mediated suppression of the LPS-bacterial response. Regarding the tissue remodeling process, the two subsets attenuated negative-regulated BMP signaling to facilitate osteoinduction and up-regulated NAMPT to establish a transient stem cell-activating niche for tissue regeneration. This study underscored the potential of functionalized GO-induced M2 sub-phenotypes as modulators in regenerative medicine.