Adenosine A(2A) Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri 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(2A) receptor activation limits inflammation and tissue damage, thereby playing an anti-inflammatory role. However, the role of the adenosine A(2A) receptor in the development of disease in SF mice remains unclear. Using a genetic approach, we found that adenosine A(2A) 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, Lactobacillus reuteri DSM 17938 treatment prolonged survival and reduced multiorgan inflammation in SF mice. In marked contrast, A(2A) receptor deletion completely blocked these beneficial effects of L. reuteri in SF mice. Altogether, these results suggest that although absence of the adenosine A(2A) receptor does not affect the development of disease in SF mice, it plays a critical role in the immunomodulation by L. reuteri in Treg-deficiency disease. The adenosine A(2A) receptor and its activation may have a role in treating other Treg dysfunction-mediated autoimmune diseases.