AUTHOR=He Baokun , Hoang Thomas K. , Tran Dat Q. , Rhoads Jon Marc , Liu Yuying TITLE=Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01680 DOI=10.3389/fimmu.2017.01680 ISSN=1664-3224 ABSTRACT=

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⋅A2A-/-) 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.