The effect of an anticancer drug, alpha-GalCer on the production of eosinophil leukocytes

What is it about?

Alpha-GalCer is an important anticancer drug. Eosinophils are a minority subtype of immune cells (leukocytes) whose functions are still little known. Alpha-CalCer usually activates another leukocyte type, invariant (i) NKT cells, but the ultimate effects of this stimulatory action will depend on the chemical messengers (cytokines, factors) released by iNKT cells, which vary in different contexts. We have found that the cytokine interferon (IFN)-gamma, released by iNKT cells, suppresses eosinophil production by activating a specific sequence of events in the cells that differentiate into eosinophils (eosinophil precursors). The critical steps in this pathway are: 1) the expression of the inducible NO synthase, an enzyme which produces the highly potent mediator NO; 2) the activation by NO of the surface molecules (death receptor and its ligand) which initiate programmed cell death in eosinophils. These observations suggest that one of the functions of iNKT cells is to control eosinophil differentiation, which opens new perspectives on complex types of immune reactions, such as those in cancer, allergy and worm-caused disease, which to a variable extent include both iNKT cells and eosinophils.

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Why is it important?

Little is known about the multiple roles of eosinophils in disease processes, and especially about whether these cells interact in the diseased tissues with other components of the immune system, to provide responses adapted to the needs of the organism (i.e., adaptive responses, presumably beneficial). The evidence we published that a newly discovered regulatory pathway operative in eosinophils is a target for the actions of the anticancer drug, Alpha-GalCer, is relevant because it provides a link between this pathway and eosinophil biology, on the one hand, and the versatile functions of iNKT cells, on the other.

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