Conveying glycan information into T‐cell homeostatic programs: a challenging role for galectin‐1 in inflammatory and tumor microenvironments

Abstract

The immune system has evolved sophisticated mechanisms composed of several checkpoints and fail-safe processes that enable it to orchestrate innate and adaptive immunity, while at the same time limiting aberrant or unfaithful T-cell function. These multiple regulatory pathways take place during the entire life-span of T cells including T-cell development, homing, activation, and differentiation. Galectin-1, an endogenous glycan-binding protein widely expressed at sites of inflammation and tumor growth, controls a diversity of immune cell processes, acting either extracellularly through specific binding to cell surface glycan structures or intracellularly through modulation of pathways that remain largely unexplored. In this review, we highlight the discoveries that have led to our current understanding of the role of galectin-1 in distinct immune cell process, particularly those associated with T-cell homeostasis. Also, we emphasize findings emerging from the study of experimental models of autoimmunity, chronic inflammation, fetomaternal tolerance, and tumor growth, which have provided fundamental insights into the critical role of galectin-1 and its specific saccharide ligands in immunoregulation. Challenges for the future will embrace the rational manipulation of galectin-1-glycan interactions both towards attenuating immune responses in autoimmune diseases, graft rejection, and recurrent fetal loss, while at the same overcoming immune tolerance in chronic infections and cancer.

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3− T Cells with a Distinct Activation and Glycosylation Profile

“…There are interesting parallels between the work reported in this study for Sn and previous studies on galectin-1, a b-galactosidebinding protein that has been widely studied for its T cell deathpromoting functions (40,41). The binding of galectin-1 to Nglycans on CD45RB was found to be dependent on the balance between a2,3-and a2,6-sialylation.…”

How does it act when soluble? Critical evaluation of mechanism of galectin-1 induced T-cell apoptosis

“…Keywords: galectin-1 -apoptosis mechanism -concentration dependence galectin-1 (gal-1), a member of the β-galactoside binding galectin superfamily plays role in regulation of viability of activated peripheral t lymphocytes and tumor t-cell lines [7,9], hence it contributes to the immunological balance in physiological and pathological situations [16]. data describing the mechanism of gal-1 induced t-cell apoptosis have been obtained using soluble, recombinant gal-1 and remained highly controversial [1,5,7,9,10,19].…”

Biological Applications of Plants and Algae Lectins: An Overview

“…Although galectins have been implicated in many biological activities, most of the functional studies reported to date link galectins to early developmental processes, such as neovascularization, regulation of immune cell homeostasis and inflammation [44,46,47]. Through deciphering glycan-containing information about host immune cells or microbial structures, galectins can modulate a diversity of signaling events that lead to cellular proliferation, survival, chemotaxis, trafficking, cytokine secretion and cell−cell communication [46,47].…”

“…Through deciphering glycan-containing information about host immune cells or microbial structures, galectins can modulate a diversity of signaling events that lead to cellular proliferation, survival, chemotaxis, trafficking, cytokine secretion and cell−cell communication [46,47].…”