Tissue-specific control of galectin-1-driven circuits during inflammatory responses

Abstract

The relevance of glycan-binding protein in immune tolerance and inflammation has been well established, mainly by studies of C-type lectins, siglecs and galectins both in experimental models and patient samples. Galectins, a family of evolutionarily conserved lectins, are characterized by sequence homology in the carbohydrate-recognition domain (CRD), atypical secretion via an ER-Golgi-independent pathway and the ability to recognize β-galactoside-containing saccharides. Galectin-1 (Gal-1), a prototype member of this family displays mainly anti-inflammatory and immunosuppressive activities, although, similar to many cytokines and growth factors, it may also trigger paradoxical pro-inflammatory effects under certain circumstances. These dual effects could be associated to tissue-, time- or context-dependent regulation of galectin expression and function, including particular pathophysiologic settings and/or environmental conditions influencing the structure of this lectin, as well as the availability of glycosylated ligands in immune cells during the course of inflammatory responses. Here, we discuss the tissue-specific role of Gal-1 as a master regulator of inflammatory responses across different pathophysiologic settings, highlighting its potential role as a therapeutic target. Further studies designed at analyzing the intrinsic and extrinsic pathways that control Gal-1 expression and function in different tissue microenvironments may contribute to design tailored therapeutic strategies aimed at positively or negatively modulate this glycan-binding protein in pathologic inflammatory conditions.

Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm

“…The dual role of Gal-1 in modulating inflammatory and vascular responses ( 6 , 10 , 21 , 22 ) prompted us to investigate the contribution of this lectin to pathological vascular remodeling in atherosclerosis and AAA. We demonstrated through a global loss-of-function approach that Gal-1 deficiency results in increased atherosclerotic burden and instability.…”

Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8 + regulatory T cells

“…Galectins, a family of endogenous glycan-binding proteins, serve as "glyco-checkpoints" that reprogram the tumor microenvironment (TME) and recalibrate tumor-driven circuits through intracellular and extracellular mechanisms (25). Galectin-1 (Gal-1), a proto-type member of this family specifically recognizes N-acetyllactosamine [LacNAc; Galβ (1-4)-GlcNAc] structures on glycosylated receptors present on the surface of different cells (26). Targeting Gal-1/glycan interactions suppresses tumor progression by thwarting tumor-immune escape (27)(28)(29), attenuating aberrant angiogenesis (30)(31)(32), preventing metastasis (33), and circumventing resistance to different anticancer therapies, including immunotherapy (34,35).…”

“…Stromal-Derived Gal-1 Impacts the Immunosuppressive Capacity of CD8 + Tregs In Vivo. Since Gal-1 is produced not only by tumor cells but also by stromal cells, including fibroblasts, endothelial cells, and immune cells (26,28,41), we next sought to evaluate the impact of stromal-derived Gal-1 by analyzing the growth of Gal-1 KD or WT CT26 tumor cells in Lgals1 −/− or WT mice (Fig. 4A).…”

Genetic LGALS1 Variants Are Associated with Heterogeneity in Galectin-1 Serum Levels in Patients with Early Arthritis

“…Galectins are lectins that bind β-galactosides carbohydrates [4] and they are among the best-studied glycan-binding proteins implicated in the regulation of inflammatory responses [5]. Galectins can participate in immune system homeostasis and rearrange several signaling pathways in different immune cells and tissues, thus modulating the inflammatory response [6].…”