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Light-induced dynamic RGD pattern for sequential modulation of macrophage phenotypes.

ABSTRACT: Due to the critical roles of macrophage in immune response and tissue repair, harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions. Although there have developed many advanced platforms with dynamic features for cell manipulation, few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages. Here, we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp (RGD) pattern. By employing a photo-patterning technique and the specific interaction between cyclodextrin (CD) and azobenzene-RGD (Azo-RGD), we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene (PEG-SH/PEG-Nor) hydrogel with dynamic RGD-patterned surface. After irradiation with 365-nm UV light, the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation. The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2 (ROCK2). Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.

SUBMITTER: Luo Y

PROVIDER: S-EPMC8089772 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDysregulation of monocyte-macrophage differentiation is a hallmark of vascular and metabolic diseases and associated with persistent low grade inflammation. Plasmalogens represent ether lipids that play a role in diabesity and previous data show diminished plasmalogen levels in obese subjects. We therefore analyzed transcriptomic and lipidomic changes during monocyte-macrophage differentiation in vitro using a bioinformatic approach.MethodsElutriated monocytes from 13 healthy donors were differentiated in vitro to macrophages using rhM-CSF under serum-free conditions. Samples were taken on days 0, 1, 4 and 5 and analyzed for their lipidomic and transcriptomic profiles.ResultsGene expression analysis showed strong regulation of lipidome-related transcripts. Enzymes involved in fatty acid desaturation and elongation were increasingly expressed, peroxisomal and ER stress related genes were induced. Total plasmalogen levels remained unchanged, while the PE plasmalogen species pattern became more similar to circulating granulocytes, showing decreases in PUFA and increases in MUFA. A partial least squares discriminant analysis (PLS/DA) revealed that PE plasmalogens discriminate the stage of monocyte-derived macrophage differentiation. Partial correlation analysis could predict novel potential key nodes including DOCK1, PDK4, GNPTAB and FAM126A that might be involved in regulating lipid and especially plasmalogen homeostasis during differentiation. An in silico transcription analysis of lipid related regulation revealed known motifs such as PPAR-gamma and KLF4 as well as novel candidates such as NFY, RNF96 and Zinc-finger proteins.ConclusionMonocyte to macrophage differentiation goes along with profound changes in the lipid-related transcriptome. This leads to an induction of fatty-acid desaturation and elongation. In their PE-plasmalogen profile macrophages become more similar to granulocytes than monocytes, indicating terminal phagocytic differentiation. Therefore PE plasmalogens may represent potential biomarkers for cell activation. For the underlying transcriptional network we were able to predict a range of novel central key nodes and underlying transcription factors using a bioinformatic approach.

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Light-induced dynamic RGD pattern for sequential modulation of macrophage phenotypes.

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