Turning 'sweet' on immunity: galectin–glycan interactions in immune tolerance and inflammation

Abstract

The function of deciphering the biological information encoded by the glycome, which is the entire repertoire of complex sugar structures expressed by cells and tissues, is assigned in part to endogenous glycan-binding proteins or lectins. Galectins, a family of animal lectins that bind N-acetyllactosamine-containing glycans, have many roles in diverse immune cell processes, including those relevant to pathogen recognition, shaping the course of adaptive immune responses and fine-tuning the inflammatory response. How do galectins translate glycan-encoded information into tolerogenic or inflammatory cell programmes? An improved understanding of the mechanisms underlying these functions will provide further opportunities for developing new therapies based on the immunoregulatory properties of this multifaceted protein family.

Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

“…28 Galectin-3 binds to the extracellular matrix in the carbohydrate-dependent manner and promotes cell adhesion by activating adhesion molecules. 10,23 Furthermore, our experiments showed significant reduction of proliferation and impairment of adhesion to fibronectincoated plates of Lt.shGal-3-transfected synovial fibroblasts (data not shown). The emerging data from studies using galectin-3-deficient mice support the role of this molecule in promoting inflammatory responses.…”

“…10,23 Galectins bind to and crosslink multiple glycoconjugates found on the cell surface, and can further trigger transmembrane signaling transductions…”

“…10 A number of intracellular functions have been reported for galectin-3, including positive growth regulatory ability on T cells. 24 While galectin-1 induces cell death, endogenous galectin-3 has anti-apoptotic function.…”

“…10 In RA, the galectin-3-binding protein was particularly expressed at sites of bone destruction and, in contrast, the expression of galectin-1 was never found at sites of joint invasion. 11 Furthermore, defective mononuclear cell apoptosis in infiltrates of synovial tissues from juvenile RA correlated with upregulation of galectin-3 and downregulation of galectin-1.…”

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…Although initially described as mediators of developmental processes, members of the galectin family are now known to play important roles in the innate and adaptive immune responses [1,2].…”