Adenosine regulation of the immune system

Adenosine is an endogenous nucleoside, released into the extracellular space in response to metabolic stress and cell damage and critically involved in the maintenance of tissue integrity by modulation of the immune system. The magnitude and duration of adenosine signaling are dictated by the expression and activity of a plethora of synthetic and catabolic enzymes as well as nucleoside transporters, which calibrate finely the concentration of this nucleoside in the biophase of specific receptors. Indeed, once released into the extracellular space, adenosine governs several aspects of immune cell functions by interaction with four G-protein-coupled cell membrane receptors, designated as A1, A2A, A2B, and A3 receptors. The engagement of such receptors, expressed heterogeneously on the surface of several immune cell populations, including neutrophils, macrophages, dendritic cells, mast cells, and lymphocytes, shapes a broad array of immune cell functions, which include cytokine production, degranulation, chemotaxis, cytotoxicity, apoptosis, and proliferation.