Adenosine A Receptor Deletion Blocks the Beneficial Effects of in Regulatory T-Deficient Scurfy Mice.

The lack of a functional Foxp3 transcription factor and regulatory T (Treg) cells causes lethal, CD4 T cell-driven autoimmune diseases in scurfy (SF) mice and humans. Recent studies have shown that adenosine A receptor activation limits inflammation and tissue damage, thereby playing an anti-inflammatory role. However, the role of the adenosine A receptor in the development of disease in SF mice remains unclear. Using a genetic approach, we found that adenosine A receptor deletion in SF mice (SF[Formula: see text]) does not affect early life events, the development of a lymphoproliferative disorder, or hyper-production of pro-inflammatory cytokines seen in the Treg-deficiency state. As shown previously, DSM 17938 treatment prolonged survival and reduced multiorgan inflammation in SF mice. In marked contrast, A receptor deletion completely blocked these beneficial effects of in SF mice. Altogether, these results suggest that although absence of the adenosine A receptor does not affect the development of disease in SF mice, it plays a critical role in the immunomodulation by in Treg-deficiency disease. The adenosine A receptor and its activation may have a role in treating other Treg dysfunction-mediated autoimmune diseases.