Much Ado about Adenosine: Adenosine Synthesis and Function in Regulatory T Cell Biology

Recent studies have reported that adenosine is a significant mediator of regulatory T cell (Treg) function. Indeed, activation of the adenosine receptor subtypes expressed by a broad range of immune and inflammatory cells attenuates inflammation in several disease models. This anti-inflammatory response is associated with an increase in intracellular cAMP that inhibits cytokine responses of many immune/inflammatory cells, including T cells and APCs. Thus, adenosine produced by Tregs can provide a paracrine feedback that shapes the host response following an immunologic provocation. This review discusses the evidence that adenosine is an integral part of Treg biology and presents some of the mechanisms that may account for its contribution to the resolution of inflammation and the regulation of the immune/inflammatory cell phenotype.