Galectin-1 Facilitates Macrophage Reprogramming and Resolution of Inflammation Through IFN-β

During the resolution of acute inflammation, macrophages undergo reprogramming from pro-inflammatory, to anti-inflammatory/reparative, and eventually to pro-resolving macrophages. Galectin-1 (Gal-1) is a bona fide pro-resolving lectin while interferon beta (IFN-beta) was recently shown to facilitate macrophage reprogramming and resolution of inflammation. In this study, we found Gal-1(null) mice exhibit a hyperinflammatory phenotype during the resolution of zymosan A-induced peritonitis but not during the early inflammatory response. This phenotype was characterized by reduced macrophage numbers, increased secretion of pro-inflammatory cytokines, such as interleukin-12 (IL-12), and reduced secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10). In addition, we found a delayed expression of the pro-resolving enzyme 12/15-lipoxygenase in macrophages and heightened levels of the inflammatory protease proteinase-3 (PR3) in peritoneal fluids from Gal-1(null) mice. Moreover, we observed sexdependent differences in the inflammatory profile of Gal-1(null) mice. Notably, we found that IFN-beta levels were reduced in resolution-phase exudates from Gal-1(null) mice. Administration of IFN-beta in vivo or ex vivo treatment was able to rescue, at least in part, the hyperinflammatory profile of Gal-1(null) mice. In particular, IFN-beta recovered a subset of F4/80(+)GR-1(+) macrophages, restored IL-12 and IL-10 secretion from macrophages to WT values and diminished abnormal peritoneal PR3 levels in Gal-1(null) mice. In conclusion, our results revealed a new Gal-1-IFN-beta axis that facilitates the resolution of inflammation and might restrain uncontrolled inflammatory disorders.