Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection

SALOME PINHO; INES ALVES; JOANA GAIFEM; GABRIEL RABINOVICH

CELLULAR & MOLECULAR IMMUNOLOGY

CHINESE SOC IMMUNOLOGY

Año: 2023

1672-7681

The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responsesagainst endogenous and exogenous insults. Disruption of these safeguard and homeostatic mechanisms can lead to unpredictableinflammatory and autoimmune responses, whereas deficiency of immune stimulatory pathways may orchestrateimmunosuppressive programs that contribute to perpetuate chronic infections, but also influence cancer development andprogression. Glycans have emerged as essential components of homeostatic circuits, acting as fine-tuners of immunologicalresponses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologicsettings. Cell surface glycans, present in cells, tissues and the extracellular matrix, have been proposed to serve as “self-associatedmolecular patterns” that store structurally relevant biological data. The responsibility of deciphering this information relies ondifferent families of glycan-binding proteins (including galectins, siglecs and C-type lectins) which, upon recognition of specificcarbohydrate structures, can recalibrate the magnitude, nature and fate of immune responses. This process is tightly regulated bythe diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellularmatrix. Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation, complex Nglycanbranching, core 2 O-glycan elongation, LacNAc extension, as well as terminal sialylation and fucosylation. Moreover, weillustrate examples that highlight the contribution of these processes to the control of immune responses and their integration withcanonical tolerogenic pathways. Finally, we discuss the power of glycans and glycan-binding proteins as a source ofimmunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.