Galectin-1 induces macrophage immunometabolic reprogramming, modulates T cell immunity and attenuates atherosclerotic plaque formation

Li, Ya; Leberzammer, Julian; Blanchet, Xavier ; Duan, Rundan; Lacy, Michael; Triantafyllidou, Vasiliki; Eckardt, Veit; Briem, Eva ; Jung, Anna Simone; Su, Rui; Guerra, Joel; Jansen, Yvonne; Hristov, Michael; Enard, Wolfgang; Bernhagen, Jürgen; Weber, Christian; Atzler, Dorothee; Bartelt, Alexander; Döring, Yvonne; Santovito, Donato; Kaltner, Herbert; Ludwig, Anna-Kristin und Hundelshausen, Philipp von (2026): Galectin-1 induces macrophage immunometabolic reprogramming, modulates T cell immunity and attenuates atherosclerotic plaque formation. In: Atherosclerosis, Bd. 413, 120608

Abstract

Background and aims

Atherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation.

Methods

Effects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe−/− mice treated with recombinant Gal-1. Complementary mouse peritoneal foam cell and in vitro macrophage and T cell culture experiments were performed to study T cell differentiation, macrophage function, polarization and energy metabolism. The impact of Gal-1 on human macrophages was further evaluated in endarterectomy specimens.

Results

Gal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10–independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1E71Q variant revealed that these effects were only partly dependent on glycan binding. Beyond IL-10, Gal-1 reshaped cytokine profiles by increasing IL-17, IL-22, and IL-23, consistent with a macrophage-driven regulatory Th17 response, alongside higher frequencies of IL-10–producing and regulatory T cells.

Conclusion

Gal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Walther-Straub-Institut für Pharmakologie und Toxikologie ; Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0021-9150
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198