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

This Review discusses the importance of galectin-glycan interactions in regulating T cell survival, activation, cytokine production and regulatory functions, as well as shaping the B cell compartment. Targeting these interactions could have important therapeutic implications for inflammation, autoimmunity and cancer. Key Points Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. Extracellularly, galectins can bind multiple glycosylated binding partners and translate glycan-encoded information into immune cell homeostatic programmes. Galectin–glycoprotein interactions form a multivalent 'lattice' that controls glycoprotein clustering and endocytosis to regulate receptor signalling and activation. Several members of the galectin family trigger intracellular signals that lead to the regulation of T cell survival. This process is controlled by the glycosylation pattern of cell surface glycoproteins, which can change markedly during activation and differentiation of immune cells. Galectin 1 and galectin 10 are over-represented in CD4 + CD25 + regulatory T (T Reg ) cells and contribute to their immunosuppressive activity. In addition, galectins contribute to shaping the B cell compartment during B cell development and differentiation. Emerging evidence in knockout mice indicates crucial roles for endogenous galectins in modulating chronic inflammation, autoimmunity and allergy. In addition, galectins can function as soluble mediators that are used by tumour cells to evade immune responses. The essential roles of galectin–glycan interactions in immune tolerance and homeostasis make them attractive therapeutic targets for limiting autoimmune inflammation, preventing allograft rejection and potentiating antitumour responses. 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