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Review
. 2019 Jan 29:10:90.
doi: 10.3389/fimmu.2019.00090. eCollection 2019.

The Role of Glycosphingolipids in Immune Cell Functions

Tao Zhang  1 , Antonius A de Waard  2   3 , Manfred Wuhrer  1 , Robbert M Spaapen  2   3
Affiliations
Review

The Role of Glycosphingolipids in Immune Cell Functions

Tao Zhang et al. Front Immunol. .

Abstract

Glycosphingolipids (GSLs) exhibit a variety of functions in cellular differentiation and interaction. Also, they are known to play a role as receptors in pathogen invasion. A less well-explored feature is the role of GSLs in immune cell function which is the subject of this review article. Here we summarize knowledge on GSL expression patterns in different immune cells. We review the changes in GSL expression during immune cell development and differentiation, maturation, and activation. Furthermore, we review how immune cell GSLs impact membrane organization, molecular signaling, and trans-interactions in cellular cross-talk. Another aspect covered is the role of GSLs as targets of antibody-based immunity in cancer. We expect that recent advances in analytical and genome editing technologies will help in the coming years to further our knowledge on the role of GSLs as modulators of immune cell function.

Keywords: cancer; differentiation; expression; glycans; glycolipids; immunity; receptors; regulation.

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Figures

Figure 1
Figure 1
Schematic diagram of the different types of GSLs. (A) Major GSLs expressed in immune cells and proposed GSL biosynthetic pathway. The key enzymes are in green. GSLs that have been given a cluster of differentiation (CD) number are annotated in red. (B) Terminal glycan motifs that have been given a CD number and the most prominent E-selectin ligand present on human neutrophils.
Figure 2
Figure 2
Schematic diagram of GSL expression in different stages of human (H) and murine (M) immune cell differentiation. GSL subsets that have been reported are represented by colored spheres, unreported subsets are represented by gray spheres. The absence of a sphere indicates that the GSL subset could not be detected. See Table 1 for details on the subset expression.
Figure 3
Figure 3
Schematic model of the different levels of GSL regulation. Input signals described to be able to affect the GSL repertoire of a cell are either cytokines, other ligands with membrane-bound receptors or ligands with intracellular receptors. These affect the GSL repertoire by changing the expression or activity of ceramide synthases such as acidic sphingomyelinase (1), nucleotide sugar synthases in the cytoplasm (2), nucleotide sugar transporters which transport the nucleotide sugars into the Golgi apparatus (3), glycosyltransferases (4), trafficking of the GSLs from the Golgi apparatus to the plasma membrane (5), or glycosidases (6).
Figure 4
Figure 4
Schematic model of the different GSL functions. Essential glycan-glycan, protein-glycan, and lipid interactions are highlighted (red dot). (A) GSLs are involved in including and (not shown) excluding proteins from microdomains. (B) Several receptors can be directly regulated by GSLs present in the cell membrane. (C) Crosslinking of several GSLs can induce signaling across the membrane. (D) GSLs can interact with glycans (CCI, left) or with proteins (PCI, right) on other cells, contributing to cell-cell recognition and adhesion.
See this image and copyright information in PMC

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