Adenosine A(2A) receptor activation limits chronic granulomatous disease-induced hyperinflammation.

Chronic granulomatous disease (CGD) is caused by defects in the NADPH oxidase complex and is characterized by an increased susceptibility to infection. Other significant complications of CGD include autoimmunity and non-infectious hyperinflammatory disorders. We show that a gp91(phox) deficiency leads to the development of phenotypically altered T lymphocytes in mice and that this abnormal, hyperactive phenotype can be modulated by activation of the adenosine A(2A) receptor. T cells isolated from CGD mice produce significantly higher levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF-α, IL-4 and IL-13 than do WT cells after TCR-mediated activation; treatment with the selective adenosine A(2A) receptor agonist, CGS21680, potently inhibits this response. Additionally, the over exuberant inflammatory response elicited by thioglycollate challenge in gp91(phox) deficient mice is attenuated by CGS21680. These data suggest that treatment with A(2A)R agonists may be an effective therapy by which to regulate the immune system hyperactivity that results from a gp91(phox) deficiency. 2010 Elsevier Inc. All rights reserved.