Regulatory T cell α(1,3)-exofucosylation for treatment of neurodegenerative diseases

α(1,3)-exofucosylation is an enzymatic process whereby the monosaccharide L-fucose is added in α(1,3)-linkage onto a pertinent acceptor glycan displayed by a cell membrane glycoprotein or glycolipid. One pertinent acceptor glycan is the terminal trisaccharide unit known as a "sialylated type 2 lactosamine". In this case, α(1,3)-exofucosylation creates the glycan motif sialylated Lewis X (sLeX, CD15 s), the canonical E-selectin binding determinant. At sites of tissue inflammation, endothelial E-selectin enables sLeX-laden blood-borne cells to migrate to, and then extravasate at, diseased sites. Thus, α(1,3)-exofucosylation facilitates T cell tissue infiltration. Considerable data demonstrate the capacity of regulatory T cells (Tregs) to suppress pro-inflammatory processes in the central nervous system. In this review, we describe how α(1,3)-exofucosylation of antigen-specific Tregs can be harnessed to optimize neuroprotection and neurorestoration for both inflammatory and neurodegenerative diseases.