generation and clearance of extracellular adenosine are critical in limiting tissue pathology, with mice genetically deficient either in the generation or clearance of extracellular adenosine displaying profound pathologies due to inappropriate control of inflammation. Extracellular adenosine mediates its biological effects through four adenosine receptors, each with distinct expression patterns and different genetic roles in regulating physiology and inflammation. Based on genetic studies, adenosine-dependent signaling can play a critical role in limiting tissue damage. Significantly, the anti-inflammatory adenosine pathway is coordinately induced following injury/inflammation, with both CD73 and adenosine receptors simultaneously induced. Furthermore, by screening for the relative activities of multiple Adoras, studies have revealed that Adora2b is a potent antiinflammatory receptor. T cells are a major cell type of the adaptive immune system that orchestrate the immune response. Within the T cell compartment, regulatory T cells serve a critical function in restraining inappropriate immune responses and inhibiting inflammation. Tregs mediate these inhibitory effects by multiple mechanisms depending on the tissue and nature of injury/inflammation -10, IL-35 and transforming growth factor -b, generation of extracellular adenosine, and cell-contact dependent mechanisms). Notably, Tregs can limit immune responses to a specific infection or insult or Tregs can have a more general, nonspecific inhibitory effect. While Tregs can achieve their fate either during development or they can differentiate from a na? ��ve T cell into an induced Treg, both cells express the transcription factor FoxP3, a critical molecular determinant essential for Treg function. Recent studies have shown that extracellular adenosine is one factor that can enhance the differentiation and function of Tregs, potentially through signaling through Adora2a. While many studies have focused on the role of Adora2a in regulating T cell function, much less is known about the contribution of Adora2b and its effects on T cell differentiation. In this study, we directly investigated the Adora2b receptor as a regulator of Treg differentiation. These studies reveal a previously unappreciated role for Adora2b in promoting Tregs both in vitro and in vivo, and identify a previously unappreciated mechanism by which Adora2b might limit inflammation. During acute inflammatory responses, the generation of extracellular adenosine is an important feedback mechanism that limits inflammation.