After the onset of inflammation in contrast to genetic ablation of Adora2b that occurred prior to the induction of inflammation. Consistent with this idea, direct comparison of acute and chronic models of bleomycin-induced lung injury demonstrated that while Adora2b served a potent anti-inflammatory role during acute lung injury, Adora2b had little effect on inflammation and was instead pro-fibrotic during chronic pulmonary fibrosis. The pathogenic potential of Adora2b in chronic inflammation is not restricted to the lung. For example, Adora2b signaling was recently revealed to be detrimental in sickle cell anemia, a context in which elevated levels of extracellular adenosine-Adora2b signaling promotes red blood cell sickling, contributing to the pathogenesis of this disease. Based on our current observations that Adora2b enhances Tregs, it is interesting to speculate that some of the detrimental effects of Adora2b in chronic pathologies may be due to excessive generation or function of Tregs. A detrimental role for an adenosine-driven Treg pathway may be particularly relevant in the context of elevated extracellular adenosine levels. In fact, recent data indicate that Tregs may participate in the process of fibrosis, with a pro-fibrotic outcome occurring through increased Treg production of TGF-b1 and subsequent collagen production following immune activation. The divergent effects of Adora2b in acute and chronic inflammatory contexts indicate that Adora2b function is likely to be shaped by the cells and environments in which inflammation is occurring. Our data define a role for Adora2b in enhancing Tregs either in primary activated murine T cell cultures or after LPS exposure, a finding consistent with a recent report showing that antagonizing Adora2b signaling inhibits the generation of Tregs in vitro. In contrast to our Tulathromycin B findings, however, a recent paper reported that Adora2b promoted the generation of pro-inflammatory Th17 cells. While the explanation for this apparent discrepancy remains to be elucidated, it is notable that the Th17promoting effects of Adora2b in these studies were isolated to effects of Adora2b specifically on dendritic cells, and not on macrophages. This observation Butylhydroxyanisole raises the possibility that the contribution of Adora2b to T cell differentiation depends on the type of antigen presenting cell and microenvironment. For example, while treatment of dendritic cells with NECA induces IL-6 expression in an Adora2b-dependent mechanism, Adora2b-deficient mice or macrophages had increased levels of IL-6 during acute inflammation, indicating that Adora2b can limit IL-6 in certain contexts.