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

Abstract

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 b (IFN-b) 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 12/15lipoxygenase 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-b levels were reduced in resolution-phase exudates from Gal-1 null mice. Administration of IFN-b 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-b 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-b axis that facilitates the resolution of inflammation and might restrain uncontrolled inflammatory disorders.

Bifidobacteria-mediated immune system imprinting early in life

“…Also, in culture experiments using fecal water from B. infantis EVC001-supplemented children, upregulation of galectin-1 was seen (Figure 6D), further suggesting that ILA-mediated signaling explains some of the effects of B. infantis EVC001 supplementation in breastfed infants. In an animal model of zymosan-induced peritonitis, galectin-1 has been reported to induce IL-27 and IL-10 and act through IFNb-dependent reprogramming of tissue macrophages and be essential in order to resolve inflammation (Yaseen et al, 2020). Our findings of HMO-metabolizing microbes and the induction of tolerogenic responses are concurrent and associated with elevated IL-27 and IFNb and ILA-mediated upregulation of galectin-1 on CD4 + T cells.…”

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

“…Gal-1, the first discovered member of the galectin family, is widely distributed in the immune system and other tissues to contribute to its crucial function ( Camby et al, 2006 ). For example, Gal-1 can facilitate macrophage reprogramming and provides a powerful anti-inflammatory effect by suppressing T cells ( Camby et al, 2006 ; Yaseen et al, 2020 ). Notably, overexpression of Gal-1 is linked to the promotion of many types of cancer progression.…”

Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits

“…Lgals1 −/− mice presented a more severe form of colitis with higher amounts of interferon-γ (IFN-γ) in cLP, and treatment with exogenous rGal1 partially attenuated this exacerbated inflammatory response through up-regulation of IL-10 and down-regulation of IFN-γ. The increase in IL-10 production may be the result of the coordinated action of distinct mechanisms responsible for orchestrating tolerogenic circuits in the gut, including the induction of type 1 T regs via activation of the cellular musculoaponeurotic fibrosarcoma (c-Maf)/aryl hydrocarbon receptor pathway ( 37 ), differentiation of tolerogenic DCs via phosphorylation of signal transducer and activator of transcription 3 ( 24 ), reprogramming of M1 inflammatory macrophages ( 38 , 39 ), and/or promotion of anti-inflammatory enterocyte programs ( 40 ). These results highlight the essential role of endogenous Gal1 as an anti-inflammatory mediator that promotes resolution of autoimmune inflammation and restores immune cell homeostasis, as has been described in models of autoimmune neuroinflammation and inflammatory arthritis ( 8 ).…”