The carbohydrate recognition by cytokines modulates their physiological activities

A variety of cytokines have been reported to be able to recognize specific carbohydrate moieties. To date, the role of carbohydrate recognition in cytokine function has been analyzed for several cytokines, including fibroblast growth factor (FGF), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2. The FGF family and their receptors have been found to recognize a heparan sulfate proteoglycan, which generates rigid complexes that induce signal transduction. We have found that IL-2 recognizes a high-mannose type glycan on the alpha subunit of the IL-2 receptor as well as a peptide portion of this subunit. Blocking this carbohydrate-IL-2 interaction diminished IL-2-induced signaling and T-cell proliferation. We have also shown that TNF-alpha recognizes the second mannose 6-phosphate diester of the glycan portion of glycosylphosphatidylinositol (GPI)-anchored glycoproteins. Blocking this GPI-anchored glycan-TNF-alpha interaction abrogates TNF-alpha-induced apoptosis. We aim to increase the number of cytokines which modulate their functions through the unique carbohydrate recognition, and open the way to systematically elucidate the biological functions of cytokine-carbohydrate interaction in immune system.