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Plasticity in biological systems is attributed to the combination of multiple parameters which determine function. These include genotypic, phenotypic, and environmental factors. While biological processes can be viewed as ordered and sequential, biological randomness was suggested to underline part of them. The present review looks into the concept of randomness in biological systems by exploring the glycosphingolipids-NKT cells example. NKT cells are a unique subset of regulatory lymphocytes which play a role in both inflammation and tolerance. Glycosphingolipids promote an immune balance by changing different arms of the immune system in opposing environments. Traditional immunology looks at skewing the immune system into different directions by different types of activation of the same cell stimulation of different cells subsets, use of different ligands, or different the effect of different immune environments. While these may explain some of the effects, the lack of consistency and opposing results under similar settings may involve randomness which may also be part of real life effects of immunomodulatory agents. It means that several of the biological processes, cannot be explained by simple linear models, and may involve more complex concepts. The application for these concepts for improving therapies to patients with Gaucher disease are discussed.   SUMMARY    The use of different ligands that target a variety of cell subsets in different immune environments may underlie differences in the functionality of NKT cells and their variability in response to NKT-based therapies. The novel concept of randomness in biology means that several biological processes cannot be solely explained by simple linear models and may instead involve much more complicated schemes of random disorder. These may have implications on future design of therapeutic regimens for improving the response to current treatments.

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems